Long non-coding RNAs, known as LncRNAs, have demonstrated a robust association with the pathogenesis of stroke. NRON and SNHG are among the most extensively studied lncRNAs in the context of atherosclerosis and inflammatory conditions. Given the absence of a current pathophysiological hypothesis regarding the potential relevance of the SNHG family and NRON lncRNAs in ischemic stroke (IS), this study aimed to investigate the altered expression of NRON and SNHG11 following atherosclerotic ischemic stroke (AIS) and their potential association with the risk of AIS. Blood samples were collected from 65 AIS patients (with large artery atherosclerosis or small vessel disease) and 65 controls. The expression levels of NRON and SNHG11 were assessed within the first 24 h following the stroke using quantitative real-time PCR. NRON expression exhibited a significant decrease in patients compared to controls, while no substantial difference was observed in the expression level of SNHG11 between the two groups. Furthermore, logistic regression analysis revealed a significant negative association between NRON expression and the risk of AIS (adjusted odds ratio = 0.70; 95% confidence interval 0.55–0.89, P = 0.004). These findings suggest that NRON may play a role in the pathogenesis of AIS and could potentially serve as a biomarker for the disease. To fully comprehend the mechanism underlying the association between NRON and AIS and to explore its potential therapeutic implications, further investigation is warranted.
{"title":"Altered expression of long non-coding RNAs NRON and SNHG11 in patients with ischemic stroke","authors":"Negin Gharbi, Hamideh Mahmoudinasab, Etrat Hooshmandi, Mousa Rahimi, Mahnaz Bayat, Najmeh Karimi, Seyedeh Shamim Hojati, Zoofa Zayani, Reza Tabrizi, Afshin Borhani-Haghighi","doi":"10.1186/s43042-024-00482-w","DOIUrl":"https://doi.org/10.1186/s43042-024-00482-w","url":null,"abstract":"Long non-coding RNAs, known as LncRNAs, have demonstrated a robust association with the pathogenesis of stroke. NRON and SNHG are among the most extensively studied lncRNAs in the context of atherosclerosis and inflammatory conditions. Given the absence of a current pathophysiological hypothesis regarding the potential relevance of the SNHG family and NRON lncRNAs in ischemic stroke (IS), this study aimed to investigate the altered expression of NRON and SNHG11 following atherosclerotic ischemic stroke (AIS) and their potential association with the risk of AIS. Blood samples were collected from 65 AIS patients (with large artery atherosclerosis or small vessel disease) and 65 controls. The expression levels of NRON and SNHG11 were assessed within the first 24 h following the stroke using quantitative real-time PCR. NRON expression exhibited a significant decrease in patients compared to controls, while no substantial difference was observed in the expression level of SNHG11 between the two groups. Furthermore, logistic regression analysis revealed a significant negative association between NRON expression and the risk of AIS (adjusted odds ratio = 0.70; 95% confidence interval 0.55–0.89, P = 0.004). These findings suggest that NRON may play a role in the pathogenesis of AIS and could potentially serve as a biomarker for the disease. To fully comprehend the mechanism underlying the association between NRON and AIS and to explore its potential therapeutic implications, further investigation is warranted.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"27 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-24DOI: 10.1186/s43042-024-00481-x
Anamika Das, Gunanidhi Dhangadamajhi
COVID-19 has its life-threatening complications more pronounced in people with underlying health conditions such as diabetes, cardiovascular disease and kidney disease. Inhibition of the sodiumglucose cotransporter 2 (SGLT2), which primarily increases urinary glucose excretion, is shown to be beneficial in patients with type 2 diabetes mellitus (T2D) and other comorbidities. SGLT2 is encoded by SLC5A2 gene, and of the several genetic variants, SNP rs9934336 is gaining importance for being associated with reduced HbA1c level and lower incidence of T2D. Since a complex bidirectional relationship exists between COVID-19 and hyperglycaemia, we conducted a worldwide association study to investigate the effect of rs9934336 on COVID-19 outcomes. Worldwide prevalence data of SLC5A2 SNP rs9934336 were obtained from relevant published articles and databases for genomic variants. COVID-19 data procured from the Worldometer website were used for conducting Spearman’s correlation analysis with minor allele frequency data of rs9934336. Significant positive correlation was observed between rs9934336 and COVID-19 incidence (p < 0.0001, r = 0.6225) as well as deaths (p < 0.0001, r = 0.5837). The present finding of significant association of SLC5A2 variant rs9934336 with COVID-19 risk has to be validated by case–control studies in diverse populations along with other variants regulating the expression and function of SGLT2.
{"title":"Association of common variant rs9934336 of SLC5A2 (SGLT2) gene with SARS-CoV-2 infection and mortality","authors":"Anamika Das, Gunanidhi Dhangadamajhi","doi":"10.1186/s43042-024-00481-x","DOIUrl":"https://doi.org/10.1186/s43042-024-00481-x","url":null,"abstract":"COVID-19 has its life-threatening complications more pronounced in people with underlying health conditions such as diabetes, cardiovascular disease and kidney disease. Inhibition of the sodiumglucose cotransporter 2 (SGLT2), which primarily increases urinary glucose excretion, is shown to be beneficial in patients with type 2 diabetes mellitus (T2D) and other comorbidities. SGLT2 is encoded by SLC5A2 gene, and of the several genetic variants, SNP rs9934336 is gaining importance for being associated with reduced HbA1c level and lower incidence of T2D. Since a complex bidirectional relationship exists between COVID-19 and hyperglycaemia, we conducted a worldwide association study to investigate the effect of rs9934336 on COVID-19 outcomes. Worldwide prevalence data of SLC5A2 SNP rs9934336 were obtained from relevant published articles and databases for genomic variants. COVID-19 data procured from the Worldometer website were used for conducting Spearman’s correlation analysis with minor allele frequency data of rs9934336. Significant positive correlation was observed between rs9934336 and COVID-19 incidence (p < 0.0001, r = 0.6225) as well as deaths (p < 0.0001, r = 0.5837). The present finding of significant association of SLC5A2 variant rs9934336 with COVID-19 risk has to be validated by case–control studies in diverse populations along with other variants regulating the expression and function of SGLT2.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"122 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Several reports discussed a connection between CD36 genotypes associated with obesity, influencing the development of Type 2 diabetes mellitus (T2DM). Therefore, this study examines the prognostic value of CD36 polymorphism rs1761667 (G/A) in individuals with obese T2DM. The investigation also explores the correlation between this genetic variation and the clinical/biochemical parameters of the subjects. Blood samples of a total of 475 subjects from north India were collected from the outpatient unit (OPD), Department of Medicine, KGMU, Lucknow as per inclusion/exclusion criteria. Anthropometric details of study subjects were recorded and biochemical parameters were estimated in 250 T2DM cases, 75 obese T2DM cases, and 150 controls. The CD36 gene variant rs1761667 (G/A) was subject to genotypic analysis using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, utilizing specific primers and HhaI enzyme. All statistical analysis was done using SPSS (ver. 21.0) and Prism (5.01) software. Fasting plasma glucose (FPG), systolic blood pressure (SBP), post-prandial glucose (PPG) were significant in T2DM subjects. Lipid profile such as Total Cholesterol (TC), Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) were also found significantly associated with obese T2DM cases. GA and AA genotypes of rs1761667 (G/A) showed significant associations in obese T2DM cases. The GA genotype demonstrated a considerable association (P < 0.001) with a 2.77-fold increased susceptibility to the high risk of T2DM. The AA genotype was found to be significantly associated (P = 0.008) with 2.94-fold higher risk of T2DM in obesity while 9.33 folds significant risk of developing obesity in T2DM cases. The risk of obesity in T2DM cases can be assessed by genotyping the CD36 genetic variant rs1761667 (G/A). However, raised FPG, PPG, TC, LDL, and VLDL showed poor prognosis in obese T2DM cases. CD36 gene variant can be proposed as a prognostic biomarker for risk prediction of T2DM and obesity, while anthro-biochemical risk factors as preventive biomarker.
{"title":"CD36 gene variant rs1761667(G/A) as a biomarker in obese type 2 diabetes mellitus cases","authors":"Ashwin Kumar Shukla, Amreen Shamsad, Atar Singh Kushwah, Shalini Singh, Kauser Usman, Monisha Banerjee","doi":"10.1186/s43042-024-00478-6","DOIUrl":"https://doi.org/10.1186/s43042-024-00478-6","url":null,"abstract":"Several reports discussed a connection between CD36 genotypes associated with obesity, influencing the development of Type 2 diabetes mellitus (T2DM). Therefore, this study examines the prognostic value of CD36 polymorphism rs1761667 (G/A) in individuals with obese T2DM. The investigation also explores the correlation between this genetic variation and the clinical/biochemical parameters of the subjects. Blood samples of a total of 475 subjects from north India were collected from the outpatient unit (OPD), Department of Medicine, KGMU, Lucknow as per inclusion/exclusion criteria. Anthropometric details of study subjects were recorded and biochemical parameters were estimated in 250 T2DM cases, 75 obese T2DM cases, and 150 controls. The CD36 gene variant rs1761667 (G/A) was subject to genotypic analysis using the polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) method, utilizing specific primers and HhaI enzyme. All statistical analysis was done using SPSS (ver. 21.0) and Prism (5.01) software. Fasting plasma glucose (FPG), systolic blood pressure (SBP), post-prandial glucose (PPG) were significant in T2DM subjects. Lipid profile such as Total Cholesterol (TC), Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) were also found significantly associated with obese T2DM cases. GA and AA genotypes of rs1761667 (G/A) showed significant associations in obese T2DM cases. The GA genotype demonstrated a considerable association (P < 0.001) with a 2.77-fold increased susceptibility to the high risk of T2DM. The AA genotype was found to be significantly associated (P = 0.008) with 2.94-fold higher risk of T2DM in obesity while 9.33 folds significant risk of developing obesity in T2DM cases. The risk of obesity in T2DM cases can be assessed by genotyping the CD36 genetic variant rs1761667 (G/A). However, raised FPG, PPG, TC, LDL, and VLDL showed poor prognosis in obese T2DM cases. CD36 gene variant can be proposed as a prognostic biomarker for risk prediction of T2DM and obesity, while anthro-biochemical risk factors as preventive biomarker. ","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"7 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.1186/s43042-024-00479-5
Teymoor Khosravi, Karim Naghipoor, Fatemeh Vaghefi, Ali Mohammad Falahati, Morteza Oladnabi
Ehlers–Danlos syndrome (EDS), osteogenesis imperfecta (OI), and cutis laxa (CL) are three rare and heterogeneous connective tissue disorders. Patients with these syndromes have similar manifestations and unpredictable prognosis, making a misdiagnosis highly probable. Some of their subtypes are inherited in autosomal recessive patterns, so they are expected to be prevalent in populations like Iran, where consanguineous marriages are common. In the current work, a cohort of Iranian patients with overlapping phenotypes of the EDS/OI/CL and their mutation spectrum was defined. Based on this, in silico analysis was conducted to anticipate further probable genetic variations. Pathogenicity of EDS, OI, and CL variants in Iranian patients was evaluated using Web servers. A protein interaction network was created by String database and visualized using a Python-based library. The Iranome database was used to predict other genetic mutations in all reported genes of EDS, OI, and CL syndromes. In the EDS/OI/CL overlap phenotype, 32 variants in 18 genes have been involved. At least 59% of patients were from families with consanguineous marriages. Interaction analysis showed that COL1A1, COL1A2, CRTAP, LEPRE1, PLOD1, and ADAMTS2 have the most significant impact within the protein network of EDS/OI/CL overlap phenotype. Analyzing the Iranome database revealed 46 variants of EDS, OI, and CL genes potentially disease causing. The overlapping phenotype of EDS, OI, and CL syndromes requires genetic testing (e.g., whole-exome sequencing) to reveal respective variants, which helps to diagnose more accurately and manage the disease more effectively. Particularly in populations with high rates of consanguineous marriages, such as Iran, genetic screening plays a crucial role in premarital and prenatal counseling to prevent the transmission of these rare connective tissue disorders.
{"title":"In silico analysis of mutation spectrum of Ehlers–Danlos, osteogenesis imperfecta, and cutis laxa overlapping phenotypes in Iranian population","authors":"Teymoor Khosravi, Karim Naghipoor, Fatemeh Vaghefi, Ali Mohammad Falahati, Morteza Oladnabi","doi":"10.1186/s43042-024-00479-5","DOIUrl":"https://doi.org/10.1186/s43042-024-00479-5","url":null,"abstract":"Ehlers–Danlos syndrome (EDS), osteogenesis imperfecta (OI), and cutis laxa (CL) are three rare and heterogeneous connective tissue disorders. Patients with these syndromes have similar manifestations and unpredictable prognosis, making a misdiagnosis highly probable. Some of their subtypes are inherited in autosomal recessive patterns, so they are expected to be prevalent in populations like Iran, where consanguineous marriages are common. In the current work, a cohort of Iranian patients with overlapping phenotypes of the EDS/OI/CL and their mutation spectrum was defined. Based on this, in silico analysis was conducted to anticipate further probable genetic variations. Pathogenicity of EDS, OI, and CL variants in Iranian patients was evaluated using Web servers. A protein interaction network was created by String database and visualized using a Python-based library. The Iranome database was used to predict other genetic mutations in all reported genes of EDS, OI, and CL syndromes. In the EDS/OI/CL overlap phenotype, 32 variants in 18 genes have been involved. At least 59% of patients were from families with consanguineous marriages. Interaction analysis showed that COL1A1, COL1A2, CRTAP, LEPRE1, PLOD1, and ADAMTS2 have the most significant impact within the protein network of EDS/OI/CL overlap phenotype. Analyzing the Iranome database revealed 46 variants of EDS, OI, and CL genes potentially disease causing. The overlapping phenotype of EDS, OI, and CL syndromes requires genetic testing (e.g., whole-exome sequencing) to reveal respective variants, which helps to diagnose more accurately and manage the disease more effectively. Particularly in populations with high rates of consanguineous marriages, such as Iran, genetic screening plays a crucial role in premarital and prenatal counseling to prevent the transmission of these rare connective tissue disorders.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"122 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-23DOI: 10.1186/s43042-024-00475-9
Brooke M. Dunleavy, Alison J. Schildt, Caitlin Harrington, David A. Stevenson
Biallelic variants in SPARC are extremely rare, and have been reported in only a few cases of autosomal recessive osteogenesis imperfecta (OI) type XVII. Here, we describe an individual with a SPARC homozygous missense variant (c.787G > A; p.Glu263Lys) and expand on the phenotype. The proband had a history of multiple fractures, osteopenia, severe thoracolumbar levoscoliosis, rib fusion, global hypotonia, conductive hearing loss, and was non-ambulatory. Several of his features were similar to previously described cases, such as early neuromuscular concerns, scoliosis, long bone and vertebral compression fractures, and delayed motor milestones, suggesting these are consistent across SPARC-related osteogenesis imperfecta (OI). However, the proband sustained fractures at a younger age with a more severe course compared to most previous reports. He also had bony fusion of several ribs and hearing loss, which have not been reported in SPARC-related OI. Overall, the proband supports the current phenotype of SPARC-related OI, but also expands the phenotypic variability.
{"title":"Osteogenesis imperfecta type XVII: expansion of the phenotype","authors":"Brooke M. Dunleavy, Alison J. Schildt, Caitlin Harrington, David A. Stevenson","doi":"10.1186/s43042-024-00475-9","DOIUrl":"https://doi.org/10.1186/s43042-024-00475-9","url":null,"abstract":"Biallelic variants in SPARC are extremely rare, and have been reported in only a few cases of autosomal recessive osteogenesis imperfecta (OI) type XVII. Here, we describe an individual with a SPARC homozygous missense variant (c.787G > A; p.Glu263Lys) and expand on the phenotype. The proband had a history of multiple fractures, osteopenia, severe thoracolumbar levoscoliosis, rib fusion, global hypotonia, conductive hearing loss, and was non-ambulatory. Several of his features were similar to previously described cases, such as early neuromuscular concerns, scoliosis, long bone and vertebral compression fractures, and delayed motor milestones, suggesting these are consistent across SPARC-related osteogenesis imperfecta (OI). However, the proband sustained fractures at a younger age with a more severe course compared to most previous reports. He also had bony fusion of several ribs and hearing loss, which have not been reported in SPARC-related OI. Overall, the proband supports the current phenotype of SPARC-related OI, but also expands the phenotypic variability.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"7 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139559781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-15DOI: 10.1186/s43042-024-00472-y
Jessy Abraham, Deepak Mahapatra, Pratishtha Agrawal, Mary Jovita James
Metabolic dysregulation leading to diabetes is a major public health concern in India. While evidence has pointed to a role for genetic factors, there is still limited knowledge regarding the specific variants that play a part in this process. Recent studies have implicated Tumor protein, p53, a well-known tumor suppressor, in maintaining metabolic homeostasis in our body. Polymorphisms that can disrupt this function are thought to increase susceptibility to diabetic and prediabetic phenotypes like Metabolic syndrome (MetS). A common polymorphism at codon 72 (rs1042522) is associated with obesity and other metabolic disorders. However, its role may vary depending on the specific population and disease context. Our study aimed to evaluate whether the polymorphism at codon 72 of p53 (rs1042522) is associated with MetS and Diabetes, in a Central Indian population. A total of 66 individuals and 63 healthy controls, identified based on the National Cholesterol Education Program (NCEP)/Adult Treatment Panel-III (ATP-III) 2001 guidelines, were enrolled in the study. The carriers expressing mutant allele “G” for arginine at codon 72 had higher weight than those having wild-type allele “C” which codes for proline (p = 0.038). The majority of the subjects were heterozygous for p53 codon 72 polymorphism though the association was not statistically significant for either MetS or diabetes. Our findings suggest that p53 codon 72 (rs1042522) varaints may trigger metabolic dysfunction by impacting weight. The polymorphism appears to confer a heterozygous advantage, as individuals with a heterozygous genotype exhibited the highest susceptibility to metabolic disease. Although further studies are required, our results for the first time indicate that the p53 codon 72 (rs1042522) polymorphism could be considered a genetic marker to predict the increased susceptibility to diabetic and prediabetic phenotypes among Central Indian population.
{"title":"Association of p53 codon 72 polymorphism with weight and metabolic diseases in a Central Indian population","authors":"Jessy Abraham, Deepak Mahapatra, Pratishtha Agrawal, Mary Jovita James","doi":"10.1186/s43042-024-00472-y","DOIUrl":"https://doi.org/10.1186/s43042-024-00472-y","url":null,"abstract":"Metabolic dysregulation leading to diabetes is a major public health concern in India. While evidence has pointed to a role for genetic factors, there is still limited knowledge regarding the specific variants that play a part in this process. Recent studies have implicated Tumor protein, p53, a well-known tumor suppressor, in maintaining metabolic homeostasis in our body. Polymorphisms that can disrupt this function are thought to increase susceptibility to diabetic and prediabetic phenotypes like Metabolic syndrome (MetS). A common polymorphism at codon 72 (rs1042522) is associated with obesity and other metabolic disorders. However, its role may vary depending on the specific population and disease context. Our study aimed to evaluate whether the polymorphism at codon 72 of p53 (rs1042522) is associated with MetS and Diabetes, in a Central Indian population. A total of 66 individuals and 63 healthy controls, identified based on the National Cholesterol Education Program (NCEP)/Adult Treatment Panel-III (ATP-III) 2001 guidelines, were enrolled in the study. The carriers expressing mutant allele “G” for arginine at codon 72 had higher weight than those having wild-type allele “C” which codes for proline (p = 0.038). The majority of the subjects were heterozygous for p53 codon 72 polymorphism though the association was not statistically significant for either MetS or diabetes. Our findings suggest that p53 codon 72 (rs1042522) varaints may trigger metabolic dysfunction by impacting weight. The polymorphism appears to confer a heterozygous advantage, as individuals with a heterozygous genotype exhibited the highest susceptibility to metabolic disease. Although further studies are required, our results for the first time indicate that the p53 codon 72 (rs1042522) polymorphism could be considered a genetic marker to predict the increased susceptibility to diabetic and prediabetic phenotypes among Central Indian population.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"49 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-08DOI: 10.1186/s43042-023-00471-5
Priyanka M. Sanghavi, Divya Chandel
Abnormal folate metabolism is a risk factor for DNA hypomethylation and chromosomal nondisjunction. MTHFR is a candidate gene for folliculogenesis and ovarian development. In the present study, we aimed to investigate the distribution of the MTHFR C677T polymorphism in individuals with primary amenorrhea and it’s association with the cytogenetic and clinical profile. The MTHFR polymorphism (C677T) was checked in 45 females with PA and 45 control females (age-matched) with regular menstrual cycles using polymerase chain reaction-restriction fragment length polymorphism. We observed the CC genotype in 84.4% (n = 38) of the control group females and 48.9% (n = 22) of the case group females, CT genotype in 13.3% (n = 6) in the control group females and 24.4% (n = 11) in the case group females (p = 0.039; χ2 value 4.253; odd ratio 0.316, 95%CI 0.103–0.973) and TT genotype in 2.2% (n = 1) in the control group females and 26.7% (n = 12) in the case group females (p = 0.000266; χ2 value 13.294; odd ratio 0.048, 95%CI 0.006–0.397). Out of 45 case group females, 26 females showed 46,XX karyotype, 4 females showed male karyotype, 3 females showed pure Turner karyotype, 2 females were mosaic Turner and the rest of the females showed structural abnormalities like deletion, isochromosome and normal variants. The serum values revealed significantly lower levels (p = 0.032) of progesterone in the individuals with the TT genotype as compared to the CC genotype and the radiology profile showed a significant role of the MTHFR gene in ovarian development (p = 0.024). We suggest that the MTHFR polymorphism (C677T) might be responsible for the chromosomal nondisjunction in monosomy X females. It also influences the progesterone level and ovarian development, thus affecting folliculogenesis and the ovarian reserve responsible for primary amenorrhea.
{"title":"MTHFR (C677T) polymorphism and its association with cytogenetic and clinical profile in individuals with primary amenorrhea","authors":"Priyanka M. Sanghavi, Divya Chandel","doi":"10.1186/s43042-023-00471-5","DOIUrl":"https://doi.org/10.1186/s43042-023-00471-5","url":null,"abstract":"Abnormal folate metabolism is a risk factor for DNA hypomethylation and chromosomal nondisjunction. MTHFR is a candidate gene for folliculogenesis and ovarian development. In the present study, we aimed to investigate the distribution of the MTHFR C677T polymorphism in individuals with primary amenorrhea and it’s association with the cytogenetic and clinical profile. The MTHFR polymorphism (C677T) was checked in 45 females with PA and 45 control females (age-matched) with regular menstrual cycles using polymerase chain reaction-restriction fragment length polymorphism. We observed the CC genotype in 84.4% (n = 38) of the control group females and 48.9% (n = 22) of the case group females, CT genotype in 13.3% (n = 6) in the control group females and 24.4% (n = 11) in the case group females (p = 0.039; χ2 value 4.253; odd ratio 0.316, 95%CI 0.103–0.973) and TT genotype in 2.2% (n = 1) in the control group females and 26.7% (n = 12) in the case group females (p = 0.000266; χ2 value 13.294; odd ratio 0.048, 95%CI 0.006–0.397). Out of 45 case group females, 26 females showed 46,XX karyotype, 4 females showed male karyotype, 3 females showed pure Turner karyotype, 2 females were mosaic Turner and the rest of the females showed structural abnormalities like deletion, isochromosome and normal variants. The serum values revealed significantly lower levels (p = 0.032) of progesterone in the individuals with the TT genotype as compared to the CC genotype and the radiology profile showed a significant role of the MTHFR gene in ovarian development (p = 0.024). We suggest that the MTHFR polymorphism (C677T) might be responsible for the chromosomal nondisjunction in monosomy X females. It also influences the progesterone level and ovarian development, thus affecting folliculogenesis and the ovarian reserve responsible for primary amenorrhea.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"38 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139408651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-05DOI: 10.1186/s43042-023-00470-6
Sara F. Saadawy, Ahmed Raafat, Walaa E. Omar
Autophagy-related genes (ATGs), associated with autophagy, contribute to the pathogenesis of many illnesses, including cancer. ATGs’ role in breast cancer (BC) is still under investigation. Therefore, the current study aimed to determine whether genetic variants in core ATGs correlate with BC prognosis and investigate their impact on protein plasma levels. This case–control study was carried out on 70 BC patients as well as 70 cancer-free controls in order to determine the association of these variants with BC risk. ATG10 (rs1864182) and ATG7 (rs1375206) polymorphisms were genotyped in whole blood samples using TaqMan SNP Genotyping Assays, and ATG7 and ATG10 levels in plasma were determined using ELISA. The results revealed that ATG7 (rs1375206) might contribute to BC, as patients with the GG genotype displayed a substantial association with BC (OR = 3.23, 95% CI 1.12–9.5) as well as a significant increase in ATG7 protein expression. For ATG7 rs1375206, genotypes GG was significantly associated with increased BC risk; carriers of the G allele frequently have a bad prognosis compared to carriers of the CC genotype (OR of mortality equals 3.01). Serum ATG 7 in the breast cancer patients’ group was significantly higher than that in the control group (p < 0.001). In contrast, carriers of the ATG10 (rs1864182) CC genotype were significant with a lower risk of BC (OR = 0.31, 95% CI 0.26–0.79) when compared with patients with AA genotype, while serum ATG 10 protein levels were decreased in patients carrying C allele (p < 0.05). Carriers of the C allele frequently have a good prognosis (OR of mortality equals 0.79) also the C allele were significantly less likely to have higher grade tumor (14.3% compared to 65.2% of A allele). Single gene polymorphisms (SNPs) within the ATG7 (rs1375206) and ATG 10 (rs1864182) are substantially correlated with BC among Egyptian females. Consequently, SNPs should be considered critical prognostic markers for distinguishing individuals with ATG7 (rs1375206) at elevated risk of developing BC as well as its progression from those with ATG 10 (rs1864182) at lower risk and the effect of these SNPs on its protein expression levels as ATG7 (rs1375206) polymorphism associated with decreased plasma ATG7 level, on the other hand, ATG 10 (rs1864182) polymorphism accompanied with increased ATG 10 plasma level.
自噬相关基因(ATGs)与自噬有关,是包括癌症在内的多种疾病的发病机理之一。ATGs在乳腺癌(BC)中的作用仍在研究中。因此,本研究旨在确定核心 ATGs 基因变异是否与乳腺癌预后相关,并调查其对蛋白血浆水平的影响。这项病例对照研究针对 70 名 BC 患者和 70 名无癌症对照者,以确定这些变异与 BC 风险的关联。使用TaqMan SNP基因分型测定法对全血样本中的ATG10(rs1864182)和ATG7(rs1375206)多态性进行基因分型,并使用ELISA测定血浆中的ATG7和ATG10水平。结果表明,ATG7(rs1375206)可能与BC有关,因为GG基因型患者与BC有很大关系(OR = 3.23,95% CI 1.12-9.5),且ATG7蛋白表达量显著增加。就 ATG7 rs1375206 而言,基因型 GG 与乳腺癌风险增加显著相关;与 CC 基因型携带者相比,G 等位基因携带者的预后往往较差(死亡率 OR 等于 3.01)。乳腺癌患者组的血清 ATG 7 明显高于对照组(P < 0.001)。相反,与 AA 基因型患者相比,ATG10(rs1864182)CC 基因型携带者罹患乳腺癌的风险较低(OR = 0.31,95% CI 0.26-0.79),而 C 等位基因携带者的血清 ATG 10 蛋白水平降低(P < 0.05)。C 等位基因携带者的预后通常较好(死亡率 OR 等于 0.79),而且 C 等位基因携带者患高级别肿瘤的几率明显较低(14.3%,而 A 等位基因携带者为 65.2%)。在埃及女性中,ATG7(rs1375206)和ATG10(rs1864182)的单基因多态性(SNPs)与乳腺癌密切相关。ATG7(rs1375206)多态性与血浆 ATG7 水平降低有关,而 ATG10(rs1864182)多态性则与 ATG 10 血浆水平升高有关。
{"title":"Diagnostic and prognostic value of single nucleotide polymorphisms in autophagy-related genes (ATG) among Egyptian patients with breast cancer disease","authors":"Sara F. Saadawy, Ahmed Raafat, Walaa E. Omar","doi":"10.1186/s43042-023-00470-6","DOIUrl":"https://doi.org/10.1186/s43042-023-00470-6","url":null,"abstract":"Autophagy-related genes (ATGs), associated with autophagy, contribute to the pathogenesis of many illnesses, including cancer. ATGs’ role in breast cancer (BC) is still under investigation. Therefore, the current study aimed to determine whether genetic variants in core ATGs correlate with BC prognosis and investigate their impact on protein plasma levels. This case–control study was carried out on 70 BC patients as well as 70 cancer-free controls in order to determine the association of these variants with BC risk. ATG10 (rs1864182) and ATG7 (rs1375206) polymorphisms were genotyped in whole blood samples using TaqMan SNP Genotyping Assays, and ATG7 and ATG10 levels in plasma were determined using ELISA. The results revealed that ATG7 (rs1375206) might contribute to BC, as patients with the GG genotype displayed a substantial association with BC (OR = 3.23, 95% CI 1.12–9.5) as well as a significant increase in ATG7 protein expression. For ATG7 rs1375206, genotypes GG was significantly associated with increased BC risk; carriers of the G allele frequently have a bad prognosis compared to carriers of the CC genotype (OR of mortality equals 3.01). Serum ATG 7 in the breast cancer patients’ group was significantly higher than that in the control group (p < 0.001). In contrast, carriers of the ATG10 (rs1864182) CC genotype were significant with a lower risk of BC (OR = 0.31, 95% CI 0.26–0.79) when compared with patients with AA genotype, while serum ATG 10 protein levels were decreased in patients carrying C allele (p < 0.05). Carriers of the C allele frequently have a good prognosis (OR of mortality equals 0.79) also the C allele were significantly less likely to have higher grade tumor (14.3% compared to 65.2% of A allele). Single gene polymorphisms (SNPs) within the ATG7 (rs1375206) and ATG 10 (rs1864182) are substantially correlated with BC among Egyptian females. Consequently, SNPs should be considered critical prognostic markers for distinguishing individuals with ATG7 (rs1375206) at elevated risk of developing BC as well as its progression from those with ATG 10 (rs1864182) at lower risk and the effect of these SNPs on its protein expression levels as ATG7 (rs1375206) polymorphism associated with decreased plasma ATG7 level, on the other hand, ATG 10 (rs1864182) polymorphism accompanied with increased ATG 10 plasma level.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"26 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139374260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-04DOI: 10.1186/s43042-023-00468-0
Hong-Lu Zhou, Dan-Dan Chen, Xiu-Ling Li
Insulin-like growth factor 2 (IGF2) mRNA-binding proteins 2 (IGF2BP2/IMP2), an RNA-binding protein encoded by the IGF2BP2 gene, exerts its influence across diverse pathological pathways. While accumulating evidence underscores the potential significance of IGF2BP2 in the tumorigenesis of specific cancers, a comprehensive pan-cancer investigation into its role remains absent. Consequently, we conducted an exhaustive exploration employing a multitude of databases to elucidate the plausible oncogenic implications of IGF2BP2. This encompassed a comprehensive scrutiny of its expression profiles, prognostic implications, association with cancer-associated fibroblast infiltration, biological functionality in distinct tumor contexts, and plausible correlations with drug sensitivities. Our findings showed that IGF2BP2 was highly expressed in some types of cancers, but presented at low levels in several cancer types. Furthermore, the role of IGF2BP2 in predicting prognosis exhibited a dichotomous interplay across varied cancer types. Remarkably, observations unveiled the cancer-associated fibroblast infiltration within specific tumors, notably encompassing breast invasive carcinoma of the luminal A subtype, kidney renal clear cell carcinoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, and prostate adenocarcinoma, and thymoma. Intriguingly, gene enrichment analyses spotlighted the co-expression of IGF2BP2 with genes implicated in pivotal biological processes, including DNA replication and recombinational repair. Our investigation intricately unveils the potential of IGF2BP2 as a versatile prognostic biomarker across diverse tumor categories. This study bridges existing knowledge gaps and augments the understanding of IGF2BP2’s intricate involvement in tumorigenesis, underscoring its significance as a prospective avenue for therapeutic intervention.
{"title":"Pan-cancer analysis identified IGF2BP2 as a potential prognostic biomarker for multiple tumor types","authors":"Hong-Lu Zhou, Dan-Dan Chen, Xiu-Ling Li","doi":"10.1186/s43042-023-00468-0","DOIUrl":"https://doi.org/10.1186/s43042-023-00468-0","url":null,"abstract":"Insulin-like growth factor 2 (IGF2) mRNA-binding proteins 2 (IGF2BP2/IMP2), an RNA-binding protein encoded by the IGF2BP2 gene, exerts its influence across diverse pathological pathways. While accumulating evidence underscores the potential significance of IGF2BP2 in the tumorigenesis of specific cancers, a comprehensive pan-cancer investigation into its role remains absent. Consequently, we conducted an exhaustive exploration employing a multitude of databases to elucidate the plausible oncogenic implications of IGF2BP2. This encompassed a comprehensive scrutiny of its expression profiles, prognostic implications, association with cancer-associated fibroblast infiltration, biological functionality in distinct tumor contexts, and plausible correlations with drug sensitivities. Our findings showed that IGF2BP2 was highly expressed in some types of cancers, but presented at low levels in several cancer types. Furthermore, the role of IGF2BP2 in predicting prognosis exhibited a dichotomous interplay across varied cancer types. Remarkably, observations unveiled the cancer-associated fibroblast infiltration within specific tumors, notably encompassing breast invasive carcinoma of the luminal A subtype, kidney renal clear cell carcinoma, ovarian serous cystadenocarcinoma, pheochromocytoma and paraganglioma, and prostate adenocarcinoma, and thymoma. Intriguingly, gene enrichment analyses spotlighted the co-expression of IGF2BP2 with genes implicated in pivotal biological processes, including DNA replication and recombinational repair. Our investigation intricately unveils the potential of IGF2BP2 as a versatile prognostic biomarker across diverse tumor categories. This study bridges existing knowledge gaps and augments the understanding of IGF2BP2’s intricate involvement in tumorigenesis, underscoring its significance as a prospective avenue for therapeutic intervention.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"17 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139096555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-03DOI: 10.1186/s43042-023-00469-z
Juan Luo, Xiaohong Chen, Hongxi Guo, Peiwei Zhao, Hui Yao, Lifang Feng, Luhong Yang
The methylcobalamin deficiency G (cblG) disorder, a rare autosomal recessive disease, is attributed to mutations in the MTR gene, resulting in heightened homocysteine levels and reduced methionine and megaloblastic anemia levels. This disease is predominantly diagnosed using MTR gene variation analysis. Herein, we report the case of a 2.1-month-old Chinese girl with the cblG disorder with poor feeding, failure to thrive, and pancytopenia, esotropia, ocular nystagmus, and hypotonia. However, in order to determine the possible genetic cause of the disease, whole-exome sequencing was adopted and detected compound-heterozygous mutations in MTR gene. One was splicing site mutation c.1812 + 3A > G and the other was missense mutation c.2405G > A (p.A802G), which were likely disease-causing mutations (DM). Variant c.1812 + 3A > G has not been reported before in the literature. Our data elucidated the genetic etiology of the patient and enriched the known spectrum of mutations in the MTR gene worldwide, offering exhaustive and invaluable insights for early diagnosis and appropriate medication of the cblG disorder.
{"title":"Novel MTR compound-heterozygous mutations in a Chinese girl with HHcy due to methionine synthase deficiency, cblG: a case report","authors":"Juan Luo, Xiaohong Chen, Hongxi Guo, Peiwei Zhao, Hui Yao, Lifang Feng, Luhong Yang","doi":"10.1186/s43042-023-00469-z","DOIUrl":"https://doi.org/10.1186/s43042-023-00469-z","url":null,"abstract":"The methylcobalamin deficiency G (cblG) disorder, a rare autosomal recessive disease, is attributed to mutations in the MTR gene, resulting in heightened homocysteine levels and reduced methionine and megaloblastic anemia levels. This disease is predominantly diagnosed using MTR gene variation analysis. Herein, we report the case of a 2.1-month-old Chinese girl with the cblG disorder with poor feeding, failure to thrive, and pancytopenia, esotropia, ocular nystagmus, and hypotonia. However, in order to determine the possible genetic cause of the disease, whole-exome sequencing was adopted and detected compound-heterozygous mutations in MTR gene. One was splicing site mutation c.1812 + 3A > G and the other was missense mutation c.2405G > A (p.A802G), which were likely disease-causing mutations (DM). Variant c.1812 + 3A > G has not been reported before in the literature. Our data elucidated the genetic etiology of the patient and enriched the known spectrum of mutations in the MTR gene worldwide, offering exhaustive and invaluable insights for early diagnosis and appropriate medication of the cblG disorder.","PeriodicalId":39112,"journal":{"name":"Egyptian Journal of Medical Human Genetics","volume":"4 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139083246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}