Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100901
Shahriar Ahmed , Ahmed Rakib , Mir Muhammad Nasir Uddin , Mohammad Safiqul Islam , S.M. Amanat Ullah , Talha Bin Emran
Purpose
This study was conducted to detect the two single-nucleotide polymorphisms (SNPs) (g.333509A > C and g.504742G > A) of the reelin (RELN) gene and to detect their association with autism spectrum disorder (ASD) in the Bangladeshi population.
Methods and materials
Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were performed to identify the SNPs, and their association with ASD was evaluated in a total of 216 Bangladeshi people, which included 108 autistic patients and 108 healthy participants.
Results
The alleles and genotype frequencies of g.333509A > C and g.504742G > A showed no significant relationship with ASD (χ2 = 0.603; p = 0.479 and χ2 = 0.274; p = 0.601, respectively).
Conclusions
Our findings indicate that these two variants of the RELN gene do not seem to be related with ASD in the Bangladeshi population. Therefore, further studies are suggested for identifying the SNPs of the RELN gene responsible for ASD in the Bangladeshi population.
{"title":"Association of reelin gene (RELN) polymorphism with autism spectrum disorder in the Bangladeshi population","authors":"Shahriar Ahmed , Ahmed Rakib , Mir Muhammad Nasir Uddin , Mohammad Safiqul Islam , S.M. Amanat Ullah , Talha Bin Emran","doi":"10.1016/j.mgene.2021.100901","DOIUrl":"10.1016/j.mgene.2021.100901","url":null,"abstract":"<div><h3>Purpose</h3><p>This study was conducted to detect the two single-nucleotide polymorphisms (SNPs) (g.333509A > C and g.504742G > A) of the reelin (<em>RELN</em>) gene and to detect their association with autism spectrum disorder (ASD) in the Bangladeshi population.</p></div><div><h3>Methods and materials</h3><p>Polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were performed to identify the SNPs, and their association with ASD was evaluated in a total of 216 Bangladeshi people, which included 108 autistic patients and 108 healthy participants.</p></div><div><h3>Results</h3><p>The alleles and genotype frequencies of g.333509A > C and g.504742G > A showed no significant relationship with ASD (χ<sup>2</sup> = 0.603; <em>p</em> = 0.479 and χ<sup>2</sup> = 0.274; <em>p</em> = 0.601, respectively).</p></div><div><h3>Conclusions</h3><p>Our findings indicate that these two variants of the <em>RELN</em> gene do not seem to be related with ASD in the Bangladeshi population. Therefore, further studies are suggested for identifying the SNPs of the <em>RELN</em> gene responsible for ASD in the Bangladeshi population.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100901"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54836205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100928
Hossam Hilal el idrissi , Afaf Ennahal
Background
The DNA methyltransferase 3B (DNMT3B) play a significant role for methylating the intragenic regions of active genes. Findings of previous studies suggested an association between the DNMT3b 579G>T single-nucleotide polymorphism (SNP) and susceptibility to various tumors. However, limited studies have examined the association of DNMT3B 579G>T polymorphism with gastric cancer risk (GC), and their results are contradictory. This meta-analysis was carried out in order to assess this association.
Methodology
We conducted a thorough literature search using in PubMed, Science Direct and Google Scholar databases for relevant studies published up to January 14, 2021. A total of 5 studies were identified and included in this work. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect model to take into account the heterogeneity between studies.
Results
We found no impact of DNMT3B 579G>T polymorphism on gastric cancer under all genetic models: Allelic model [G vs T, odds ratio (OR) = 0.79, 95% confidence of interval (CI): 0.55–1.13, p = 0.20], recessive model [GG vs GT + TT, OR = 0.96, 95% CI: 0.63–1.46, p = 0.86], dominant model [GG + GT vs TT, OR = 0.72, 95% CI: 0.47–1.10, p = 0.13], heterozygous model [GT vs TT, OR = 0.70, 95% CI: 0.45–1.08, p = 0.11] and homozygous model [GT vs TT, OR = 0.72, 95% CI: 0.44–1.17, p = 0.18], homozygous, OR: 0.72, 95% CI = 0.44–1.17, p = 0.18).
Conclusion
Our results indicated that DNMT3B 579G>T is not associated with GC, and it may not be used as a stratification marker to predict susceptibility.
DNA甲基转移酶3B (DNMT3B)在活性基因的基因内区域甲基化中起着重要作用。先前的研究结果表明,DNMT3b 579G>T单核苷酸多态性(SNP)与多种肿瘤的易感性之间存在关联。然而,关于DNMT3B 579G>T多态性与胃癌风险(GC)相关性的研究有限,且研究结果相互矛盾。本荟萃分析是为了评估这种关联。方法:我们使用PubMed、Science Direct和b谷歌Scholar数据库对截至2021年1月14日发表的相关研究进行了全面的文献检索。本研究共确定并纳入了5项研究。使用固定效应或随机效应模型估计95% ci的合并奇数率(or),以考虑研究之间的异质性。种能阻碍DNMT3B ResultsWe没有发现影响579 g> T多态性在胃癌遗传模型:等位基因模型(G和T比值比(或)= 0.79,95%可信区间(CI): 0.55 - -1.13, p = 0.20),隐性模型(GG vs GT + TT,或= 0.96,95%置信区间CI: 0.63 - -1.46, p = 0.86),占主导地位的模式(GG + GT vs TT,或= 0.72,95%置信区间CI: 0.47 - -1.10, p = 0.13),杂合的模型(GT和TT或= 0.70,95%置信区间CI: 0.45 - -1.08, p = 0.11)和纯合模型(GT和TT或= 0.72,95%置信区间CI:0.44 - -1.17, p = 0.18),纯合子,或者:0.72,95% CI -1.17 = 0.44, p = 0.18)。结论DNMT3B 579G>T与胃癌无相关性,不能作为预测胃癌易感性的分层标记。
{"title":"Association between DNMT3b 579G>T polymorphism and susceptibility to gastric cancer risk: A systematic review and an update meta-analysis","authors":"Hossam Hilal el idrissi , Afaf Ennahal","doi":"10.1016/j.mgene.2021.100928","DOIUrl":"10.1016/j.mgene.2021.100928","url":null,"abstract":"<div><h3>Background</h3><p>The DNA methyltransferase 3B (DNMT3B) play a significant role for methylating the intragenic regions of active genes. Findings of previous studies suggested an association between the DNMT3b 579G>T single-nucleotide polymorphism (SNP) and susceptibility to various tumors. However, limited studies have examined the association of DNMT3B 579G>T polymorphism with gastric cancer risk (GC), and their results are contradictory. This meta-analysis was carried out in order to assess this association.</p></div><div><h3>Methodology</h3><p>We conducted a thorough literature search using in PubMed, Science Direct and Google Scholar databases for relevant studies published up to January 14, 2021. A total of 5 studies were identified and included in this work. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect model to take into account the heterogeneity between studies.</p></div><div><h3>Results</h3><p>We found no impact of DNMT3B 579G>T polymorphism on gastric cancer under all genetic models: Allelic model [G vs T, odds ratio (OR) = 0.79, 95% confidence of interval (CI): 0.55–1.13, <em>p</em> = 0.20], recessive model [GG vs GT + TT, OR = 0.96, 95% CI: 0.63–1.46, <em>p</em> = 0.86], dominant model [GG + GT vs TT, OR = 0.72, 95% CI: 0.47–1.10, <em>p</em> = 0.13], heterozygous model [GT vs TT, OR = 0.70, 95% CI: 0.45–1.08, <em>p</em> = 0.11] and homozygous model [GT vs TT, OR = 0.72, 95% CI: 0.44–1.17, <em>p</em> = 0.18], homozygous, OR: 0.72, 95% CI = 0.44–1.17, p = 0.18).</p></div><div><h3>Conclusion</h3><p>Our results indicated that DNMT3B 579G>T is not associated with GC, and it may not be used as a stratification marker to predict susceptibility.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100928"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46586946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matrix metalloproteinases - 2 (MMP2) protein stimulates multiple processes involving the nervous system, vascularization, and metastasis. Mutations in MMP2 is linked to Winchester and Nodulosis-Arthropathy-Osteolysis (NAO) syndromes. In this extensive investigation, we performed a computational analysis of 114 missense Single Nucleotide Polymorphisms (SNPs) of MMP2 protein using various in-silico algorithms. A total of 21 highly deleterious and pathogenic missense SNPs (T86K, R146H, A167T, G216E, R252P, R252L D326V, D326Y, G346S, G367S, R368L, S396R, A408P, R482C, P517L, A522E, E525K, Y543C, Y552S, K579M, M598T) were identified that probably could alter the structural and functional configuration of MMP2 gene. Moreover, conservation analysis, protein stability, TM-score and RMSD calculation, protein structure prediction and superimposition, ligand binding site prediction, protein-protein interaction, protein-ligand, and protein-protein docking studies were carried out. ConSurf analysis showed seventeen missense variants in the highly conserved regions, which were predicted as highly deleterious and pathogenic by eight in-silico platforms. Furthermore, G367S and K579M showed a greater impact on stability, structural alterations, protein-ligand and protein-protein interactions. This study will help in developing target-dependent medication for diseases and could enhance the understanding of the significance of uncharacterized missense SNPs and their interrelation with the disease. This study also contemplates the computational perception into the high-risk missense SNPs on protein structural and functional configuration.
{"title":"Computational analysis of missense variants in MMP2 gene linked with Winchester syndrome and Nodulosis-Arthropathy-Osteolysis reveals structural shift in protein-protein and protein-ligand complexes","authors":"Nithya Rangasamy , Nachimuthu Senthil Kumar , Santhy K.S.","doi":"10.1016/j.mgene.2021.100931","DOIUrl":"10.1016/j.mgene.2021.100931","url":null,"abstract":"<div><p>Matrix metalloproteinases - 2 (MMP2) protein stimulates multiple processes involving the nervous system, vascularization, and metastasis. Mutations in MMP2 is linked to Winchester and Nodulosis-Arthropathy-Osteolysis (NAO) syndromes. In this extensive investigation, we performed a computational analysis of 114 missense Single Nucleotide Polymorphisms (SNPs) of MMP2 protein using various <em>in-silico</em> algorithms. A total of 21 highly deleterious and pathogenic missense SNPs (T86K, R146H, A167T, G216E, R252P, R252L D326V, D326Y, G346S, G367S, R368L, S396R, A408P, R482C, P517L, A522E, E525K, Y543C, Y552S, K579M, M598T) were identified that probably could alter the structural and functional configuration of <em>MMP2</em> gene. Moreover, conservation analysis, protein stability, TM-score and RMSD calculation, protein structure prediction and superimposition, ligand binding site prediction, protein-protein interaction, protein-ligand, and protein-protein docking studies were carried out. ConSurf analysis showed seventeen missense variants in the highly conserved regions, which were predicted as highly deleterious and pathogenic by eight <em>in-silico</em> platforms. Furthermore, G367S and K579M showed a greater impact on stability, structural alterations, protein-ligand and protein-protein interactions. This study will help in developing target-dependent medication for diseases and could enhance the understanding of the significance of uncharacterized missense SNPs and their interrelation with the disease. This study also contemplates the computational perception into the high-risk missense SNPs on protein structural and functional configuration.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100931"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100931","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47042758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Schizophrenia is a chronic serious neuropsychiatric disorder with a prevalence of 1% worldwide. Neurogenic locus NOTCH homolog protein 4 known as the NOTCH4 gene is located on chromosome 6p. NOTCH4 protein is a transmembrane protein that plays a major role in cell signaling pathways and cell differentiation. NOTCH4 SNP rs367398 is located in the gene's largest intron, intron 18, which is an area of known importance in transcriptional regulation and may be related to schizophrenia. Although many studies have shown the association of NOTCH4 polymorphism with schizophrenia, the exact molecular mechanism behind this still unknown. This study was aimed to determine the frequency of NOTCH4 rs367398 & rs387071 polymorphism and its association with schizophrenia. In total, 150 schizophrenia patients and 100 healthy controls were recruited from psychiatry department after obtaining written informed consent. NOTCH4 polymorphism was genotyped using PCR-RFLP. Positive and Negative Syndrome Scale (PANSS) and Global assessment of functioning (GAF) were used to assess the severity of schizophrenia. Both the NOTCH4 rs367398 & rs387071 genotypes were significantly associated with schizophrenia. On gender based analysis, the rs387071 was significantly associated with schizophrenia in males and whereas the rs367398 is associated with females of the study group. Further, the haplotype analysis has also supported the association of NOTCH4 locus with schizophrenia (Global haplotype association p = 0.021). The findings of the study suggest that the NOTCH4 polymorphism is significantly associated with schizophrenia in Indian population. These SNPs might also have an important role in the symptomatology of the disease.
精神分裂症是一种慢性严重神经精神疾病,全球患病率为1%。神经源性位点NOTCH同源蛋白4被称为NOTCH4基因位于染色体6p上。NOTCH4蛋白是一种跨膜蛋白,在细胞信号通路和细胞分化中起重要作用。NOTCH4 SNP rs367398位于该基因最大的内含子内含子18中,这是一个已知的转录调控重要区域,可能与精神分裂症有关。尽管许多研究表明NOTCH4多态性与精神分裂症有关,但其确切的分子机制尚不清楚。本研究旨在确定NOTCH4 rs367398 &Rs387071多态性及其与精神分裂症的关系在获得书面知情同意后,从精神科共招募精神分裂症患者150名和健康对照100名。采用PCR-RFLP对NOTCH4多态性进行基因分型。采用阳性和阴性症状量表(PANSS)和整体功能评估(GAF)来评估精神分裂症的严重程度。NOTCH4 rs367398 &Rs387071基因型与精神分裂症显著相关。在基于性别的分析中,rs387071与男性的精神分裂症显著相关,而rs367398与研究组的女性相关。此外,单倍型分析也支持NOTCH4位点与精神分裂症的关联(全局单倍型关联p = 0.021)。研究结果表明,NOTCH4多态性与印度人群的精神分裂症显著相关。这些snp也可能在疾病的症状学中起重要作用。
{"title":"Association of the NOTCH4 gene polymorphism with schizophrenia in the Indian population","authors":"Kiran Kumar PVSN , Prasenjit Mitra , Raghumoy Ghosh , SaiKiran Gangam , Shailja Sharma , Naresh Nebhinani , Praveen Sharma","doi":"10.1016/j.mgene.2021.100903","DOIUrl":"10.1016/j.mgene.2021.100903","url":null,"abstract":"<div><p>Schizophrenia is a chronic serious neuropsychiatric disorder with a prevalence of 1% worldwide. Neurogenic locus NOTCH homolog protein 4 known as the NOTCH4 gene is located on chromosome 6p. NOTCH4 protein is a transmembrane protein that plays a major role in cell signaling pathways and cell differentiation. NOTCH4 SNP rs367398 is located in the gene's largest intron, intron 18, which is an area of known importance in transcriptional regulation and may be related to schizophrenia. Although many studies have shown the association of NOTCH4 polymorphism with schizophrenia, the exact molecular mechanism behind this still unknown. This study was aimed to determine the frequency of NOTCH4 rs367398 & rs387071 polymorphism and its association with schizophrenia. In total, 150 schizophrenia patients and 100 healthy controls were recruited from psychiatry department after obtaining written informed consent. NOTCH4 polymorphism was genotyped using PCR-RFLP. Positive and Negative Syndrome Scale (PANSS) and Global assessment of functioning (GAF) were used to assess the severity of schizophrenia. Both the NOTCH4 rs367398 & rs387071 genotypes were significantly associated with schizophrenia. On gender based analysis, the rs387071 was significantly associated with schizophrenia in males and whereas the rs367398 is associated with females of the study group. Further, the haplotype analysis has also supported the association of NOTCH4 locus with schizophrenia (Global haplotype association <em>p</em> = 0.021). The findings of the study suggest that the NOTCH4 polymorphism is significantly associated with schizophrenia in Indian population. These SNPs might also have an important role in the symptomatology of the disease.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100903"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100903","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54836229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Previous studies suggested, variations in the IL28B gene can serve as predictors of sustained and rapid virological responses (SVR and RVR) in the treatment of HCV with pegylated interferon and ribavirin (pegINF-RBV) among HCV-HIV co-infected patients. Here, we explored the correlation between IL28B variants (rs12979860, rs8099917 and rs12980275) and treatment response for HCV among co-infected individuals using meta-analysis.
Methods
Relevant studies were retrieved from PubMed, EBSCO, ISI Web of Knowledge, Cochrane databases, and the role of IL28B variants on SVR and RVR in co-infected patients treated with pegINF-RBV was evaluated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fixed- and random-effects models.
Results
Forty-three studies consisting 3499 patients who achieved SVR/RVR and 4308 non-responders were included in our study. The CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, were associated with SVR in the recessive model for all HCV genotypes: rs12979860, OR = 3.18 [95% CI (2.66, 3.79)]; P < 0.0001; rs8099917, OR = 3.6`9 [95% CI (2.74, 4.97)]; P < 0.0001; rs12980275, OR = 2.97 [95% CI (2.26, 3.89)]; P < 0.0001. Significant association of rs12979860 CC genotype with RVR was also found: OR = 2.31 [95% CI (1.54, 3.57)]; P < 0.0001. Stratification analysis of HCV genotypes revealed similar trends of association with the rs12979860 CC genotype for HCV-1, HCV-1/4 and HCV-4, but no association was found for HCV-2/3 and HCV-3.
Conclusions
Our meta-analysis suggests that the CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, are strong predictors for SVR, and the rs12979860 CC genotype has significant RVR predictive value in HCV-HIV co-infected patients treated with pegINF-RBV.
先前的研究表明,在HCV- hiv合并感染患者中,il - 28b基因的变异可以作为持续和快速的病毒学反应(SVR和RVR)的预测因子。在这里,我们通过荟萃分析探讨了IL28B变异(rs12979860、rs8099917和rs12980275)与共感染个体HCV治疗反应之间的相关性。方法从PubMed、EBSCO、ISI Web of Knowledge、Cochrane数据库中检索相关研究,评估IL28B变异对pegif - rbv合并感染患者SVR和RVR的影响。通过固定效应和随机效应模型计算优势比(ORs)和95%置信区间(ci)。结果共纳入43项研究,3499例达到SVR/RVR的患者和4308例无应答者。在所有HCV基因型的隐性模型中,IL28B rs12979860、rs8099917和rs12980275的CC、TT和AA基因型分别与SVR相关:rs12979860, OR = 3.18 [95% CI (2.66, 3.79)];P & lt;0.0001;rs8099917, OR = 3.6 ' 9 [95% CI (2.74, 4.97)];P & lt;0.0001;rs12980275, OR = 2.97 [95% CI (2.26, 3.89)];P & lt;0.0001. rs12979860 CC基因型与RVR也存在显著相关性:OR = 2.31 [95% CI (1.54, 3.57)];P & lt;0.0001. HCV基因型的分层分析显示,HCV-1、HCV-1/4和HCV-4与rs12979860 CC基因型的关联趋势相似,但HCV-2/3和HCV-3与rs12979860 CC基因型无相关性。结论meta分析显示,il - 28b rs12979860、rs8099917和rs12980275基因型CC、TT和AA基因型分别是SVR的强预测因子,rs12979860基因型CC基因型在pegif - rbv治疗的HCV-HIV合并感染患者中具有显著的RVR预测价值。
{"title":"Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis","authors":"Nirmal Kumar , Suchitra S. Prabhu , Isha Monga , Indranil Banerjee","doi":"10.1016/j.mgene.2021.100909","DOIUrl":"10.1016/j.mgene.2021.100909","url":null,"abstract":"<div><h3>Background</h3><p>Previous studies suggested, variations in the <em>IL28B</em> gene can serve as predictors of sustained and rapid virological responses (SVR and RVR) in the treatment of HCV with pegylated interferon and ribavirin (pegINF-RBV) among HCV-HIV co-infected patients. Here, we explored the correlation between <em>IL28B</em> variants (rs12979860, rs8099917 and rs12980275) and treatment response for HCV among co-infected individuals using meta-analysis.</p></div><div><h3>Methods</h3><p>Relevant studies were retrieved from PubMed, EBSCO, ISI Web of Knowledge, Cochrane databases, and the role of <em>IL28B</em> variants on SVR and RVR in co-infected patients treated with pegINF-RBV was evaluated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fixed- and random-effects models.</p></div><div><h3>Results</h3><p>Forty-three studies consisting 3499 patients who achieved SVR/RVR and 4308 non-responders were included in our study. The CC, TT and AA genotypes of <em>IL28B</em> rs12979860, rs8099917 and rs12980275, respectively, were associated with SVR in the recessive model for all HCV genotypes: rs12979860, OR = 3.18 [95% CI (2.66, 3.79)]; <em>P</em> < 0.0001; rs8099917, OR = 3.6`9 [95% CI (2.74, 4.97)]; <em>P</em> < 0.0001; rs12980275, OR = 2.97 [95% CI (2.26, 3.89)]; <em>P</em> < 0.0001. Significant association of rs12979860 CC genotype with RVR was also found: OR = 2.31 [95% CI (1.54, 3.57)]; <em>P</em> < 0.0001. Stratification analysis of HCV genotypes revealed similar trends of association with the rs12979860 CC genotype for HCV-1, HCV-1/4 and HCV-4, but no association was found for HCV-2/3 and HCV-3.</p></div><div><h3>Conclusions</h3><p>Our meta-analysis suggests that the CC, TT and AA genotypes of <em>IL28B</em> rs12979860, rs8099917 and rs12980275, respectively, are strong predictors for SVR, and the rs12979860 CC genotype has significant RVR predictive value in HCV-HIV co-infected patients treated with pegINF-RBV.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100909"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100909","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43712843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100896
M. Tiwari , M.K. Verma , P.K. Singh , D. Bharti
Purpose
Study aim to investigate the possible role of Fok I VDR polymorphism in TB risk assessment.
Methods
To investigate the role of Fok I VDR polymorphism in TB risk assessment, we collected a blood sample from 106 healthy individuals including both gender. The genomic DNA was isolated and the VDR gene was amplified using gene-specific primers using polymerase chain reaction. The Genotyping of the Fok I polymorphism was performed using Fok I restriction enzyme. The distribution of genotype frequencies of VDR gene polymorphisms was calculated using Hardy-Weinberg equilibrium calculator.
Results
In the present investigation, the VDR gene was amplified with an undigested DNA band of 265 bp as FF homozygote. Additionally, 169 bp and 96 bp as ff homozygote and three bands ((265 bp, 169 bp, and 96 bp) were observed in the heterozygote. As per our finding, we report a significantly low frequency of susceptible genotypes in Ff (27.4%) and ff (6.6%) compared to average frequency Ff = 41.80% and ff = 8.25% of India. We also reported here the low frequency of mutant allele f in India's central part, i.e., Bhopal division, Madhya Pradesh. Considering our finding, the mutant allele's low frequency in central India, Madhya Pradesh, shows a negligible contribution of Fok I VDR polymorphism in TB prevalence.
Conclusions
In a comparative analysis with the Northern and Southern India population based on previous reports, the involvement of FoK I polymorphism in the VDR gene was non-significant in Central India. All the studied populations were found in Hardy-Weinberg equilibrium except North India for the Fok1 VDR genotypes.
目的探讨Fok I VDR多态性在结核病风险评估中的可能作用。方法为了研究Fok I VDR多态性在结核病风险评估中的作用,我们采集了106例健康人群(包括男女)的血液样本。分离基因组DNA,利用基因特异性引物聚合酶链反应扩增VDR基因。利用霍克1限制性内切酶对霍克1多态性进行基因分型。利用Hardy-Weinberg平衡计算器计算VDR基因多态性的基因型频率分布。结果VDR基因扩增得到一条265 bp的未消化DNA带,为FF纯合子。纯合子为169 bp和96 bp,杂合子为265 bp、169 bp和96 bp三个条带。根据我们的发现,我们报告了Ff(27.4%)和Ff(6.6%)的易感基因型频率显著低于印度的平均频率Ff = 41.80%和Ff = 8.25%。我们还报道了印度中部,即中央邦博帕尔地区突变等位基因的低频率。考虑到我们的发现,突变等位基因在印度中部中央邦的低频率表明,Fok I VDR多态性对结核病患病率的贡献可以忽略不计。结论在以往报道的基础上,通过与印度北部和南部人群的比较分析,发现FoK I多态性与VDR基因的关系在印度中部地区不显著。除印度北部的Fok1 VDR基因型外,所有研究群体均处于Hardy-Weinberg平衡状态。
{"title":"Role of Fok I VDR polymorphism in TB risk assessment; A Study in Central India population","authors":"M. Tiwari , M.K. Verma , P.K. Singh , D. Bharti","doi":"10.1016/j.mgene.2021.100896","DOIUrl":"10.1016/j.mgene.2021.100896","url":null,"abstract":"<div><h3>Purpose</h3><p>Study aim to investigate the possible role of <em>Fok</em> I VDR polymorphism in TB risk assessment.</p></div><div><h3>Methods</h3><p>To investigate the role of Fok I VDR polymorphism in TB risk assessment, we collected a blood sample from 106 healthy individuals including both gender. The genomic DNA was isolated and the VDR gene was amplified using gene-specific primers using polymerase chain reaction. The Genotyping of the <em>Fok</em> I polymorphism was performed using Fok I restriction enzyme. The distribution of genotype frequencies of VDR gene polymorphisms was calculated using Hardy-Weinberg equilibrium calculator.</p></div><div><h3>Results</h3><p>In the present investigation, the VDR gene was amplified with an undigested DNA band of 265 bp as FF homozygote. Additionally, 169 bp and 96 bp as ff homozygote and three bands ((265 bp, 169 bp, and 96 bp) were observed in the heterozygote. As per our finding, we report a significantly low frequency of susceptible genotypes in Ff (27.4%) and ff (6.6%) compared to average frequency Ff = 41.80% and ff = 8.25% of India. We also reported here the low frequency of mutant allele f in India's central part, i.e., Bhopal division, Madhya Pradesh. Considering our finding, the mutant allele's low frequency in central India, Madhya Pradesh, shows a negligible contribution of <em>Fok</em> I VDR polymorphism in TB prevalence.</p></div><div><h3>Conclusions</h3><p>In a comparative analysis with the Northern and Southern India population based on previous reports, the involvement of FoK I polymorphism in the VDR gene was non-significant in Central India. All the studied populations were found in Hardy-Weinberg equilibrium except North India for the Fok1 VDR genotypes.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100896"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45831053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100912
Demes Chornelia Martantiningtyas , Pramudji Hastuti , Ahmad Hamim Sadewa
Purpose
Ghrelin is found as an endogenous ligand for growth hormone secretagogue receptor (GHSR). Several studies have reported an association between plasma ghrelin and GHRL-single nucleotide polymorphism, namely the Leu72Met polymorphism, with Body mass Index, type 2 diabetes mellitus, and insulin resistance. The role of gene variant of GHRL Leu72Met in obesity is still unclear. The aim of the present study was to examine the associations of Leu72Met with ghrelin levels, insulin secretion, and obesity among Javanese subjects.
Materials and methods
All subjects were measured with anthropometry, and fasting blood glucose was measured by the glucose oxidase-phenol and 4 aminophenazone method. Plasma insulin and ghrelin were measured using ELISA. Insulin secretion was calculated using HOMA analysis. The Leu72Met genetic variant of the ghrelin gene was screened using PCR-RFLP.
Results
Plasma ghrelin concentrations were lower in the obese group than the lean group (P < 0.05). Fasting plasma ghrelin was negatively correlated with body mass index and insulin secretion. Subjects with the Met72 allele carried a higher risk of obesity than the subjects with the Leu72 allele (OR = 4.928 [95% CI = 2.424–10.01]).
Conclusion
The conclusion of this study is Leu72Met polymorphisms increases the risk of obesity in Javanese ethnicity, but this polymorphism does not play a role in plasma ghrelin secretion and plasma insulin secretion.
{"title":"Leu72Met polymorphism of GHRL gene increase the risk factor of obesity in a Javanese ethnic group from Indonesia","authors":"Demes Chornelia Martantiningtyas , Pramudji Hastuti , Ahmad Hamim Sadewa","doi":"10.1016/j.mgene.2021.100912","DOIUrl":"10.1016/j.mgene.2021.100912","url":null,"abstract":"<div><h3>Purpose</h3><p>Ghrelin is found as an endogenous ligand for growth hormone secretagogue receptor (GHSR). Several studies have reported an association between plasma ghrelin and GHRL-single nucleotide polymorphism, namely the Leu72Met polymorphism, with Body mass Index, type 2 diabetes mellitus, and insulin resistance. The role of gene variant of GHRL Leu72Met in obesity is still unclear. The aim of the present study was to examine the associations of Leu72Met with ghrelin levels, insulin secretion, and obesity among Javanese subjects.</p></div><div><h3>Materials and methods</h3><p>All subjects were measured with anthropometry, and fasting blood glucose was measured by the <em>glucose</em> oxidase-phenol and 4 aminophenazone method. Plasma insulin and ghrelin were measured using ELISA. Insulin secretion was calculated using HOMA analysis. The Leu72Met genetic variant of the ghrelin gene was screened using PCR-RFLP.</p></div><div><h3>Results</h3><p>Plasma ghrelin concentrations were lower in the obese group than the lean group (<em>P</em> < 0.05). Fasting plasma ghrelin was negatively correlated with body mass index and insulin secretion. Subjects with the Met72 allele carried a higher risk of obesity than the subjects with the Leu72 allele (OR = 4.928 [95% CI = 2.424–10.01]).</p></div><div><h3>Conclusion</h3><p>The conclusion of this study is Leu72Met polymorphisms increases the risk of obesity in Javanese ethnicity, but this polymorphism does not play a role in plasma ghrelin secretion and plasma insulin secretion.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100912"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49595084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100938
Ananda Vayaravel Cassinadane , Ramesh Ramasamy , M. Lenin , Kuzhandai Velu , Shaik Anwar Hussain
Background
Long-term administration of metformin in Type 2 Diabetes mellitus (T2DM), interferes with the absorption of vitamin B12 resulting in deficiency. Low levels of vitamin B12 are associated with cardiovascular morbidity and mortality in T2DM patients. Several genetic variants are associated with vitamin B12 deficiency; one among them is Methylene Tetrahydrofolate reductase (MTHFR). We analyzed MTHFR (rs180133) polymorphism and its association with metformin induced vitamin B12 deficiency in T2DM patients.
Methods
Three hundred T2DM patients were included. For the study and they were screened for vitamin B12 deficiency markers – Methyl malonic acid (MMA), Homocysteine (Hcy) and high sensitive C reactive protein (hsCRP). Genetic variant was analyzed by ARMS-PCR method. Data was analyzed with various statistical tools like ROC, Odds ratio and Likelihood ratio.
Results
There is significant reduction in folic acid and vitamin B12 in metformin users. HsCRP, Hcy and MMA are significantly increased with P < 0.001 in patients with metformin induced B12 deficiency. T allele in MTHFR (T allele ORs =2.1, TT genotype =3.6) showed risk of vitamin B12 deficiency in T2DM patients on metformin therapy. MTHFR gene polymorphism of TT genotype had a Likelihood ratio (LR) of 2.46 for folic acid, 2.77 for MMA and 3.38 for Hcy.
Conclusion
We found an association between MTHFR rs180133, 677C > T and vitamin B12 status in T2DM patients on metformin therapy. Folic acid, MMA and Hcy were found to have high specificity in concordance with MTHFR which showed to be a good predictor for vitamin B12 deficiency in T2DM patients on metformin therapy.
{"title":"Association of MTHFR (rs 1801133) gene polymorphism with biochemical markers of B12 deficiency in type 2 diabetes mellitus patients on metformin therapy","authors":"Ananda Vayaravel Cassinadane , Ramesh Ramasamy , M. Lenin , Kuzhandai Velu , Shaik Anwar Hussain","doi":"10.1016/j.mgene.2021.100938","DOIUrl":"10.1016/j.mgene.2021.100938","url":null,"abstract":"<div><h3>Background</h3><p>Long-term administration of metformin in Type 2 Diabetes mellitus (T2DM), interferes with the absorption of vitamin B12 resulting in deficiency. Low levels of vitamin B12 are associated with cardiovascular morbidity and mortality in T2DM patients. Several genetic variants are associated with vitamin B12 deficiency; one among them is Methylene Tetrahydrofolate reductase (<em>MTHFR)</em>. We analyzed <em>MTHFR</em> (rs180133) polymorphism and its association with metformin induced vitamin B12 deficiency in T2DM patients.</p></div><div><h3>Methods</h3><p>Three hundred T2DM patients were included. For the study and they were screened for vitamin B12 deficiency markers – Methyl malonic acid (MMA), Homocysteine (Hcy) and high sensitive C reactive protein (hsCRP). Genetic variant was analyzed by ARMS-PCR method. Data was analyzed with various statistical tools like ROC, Odds ratio and Likelihood ratio.</p></div><div><h3>Results</h3><p>There is significant reduction in folic acid and vitamin B12 in metformin users. HsCRP, Hcy and MMA are significantly increased with <em>P</em> < 0.001 in patients with metformin induced B12 deficiency. T allele in <em>MTHFR</em> (T allele ORs =2.1, TT genotype =3.6) showed risk of vitamin B12 deficiency in T2DM patients on metformin therapy. <em>MTHFR</em> gene polymorphism of TT genotype had a Likelihood ratio (LR) of 2.46 for folic acid, 2.77 for MMA and 3.38 for Hcy.</p></div><div><h3>Conclusion</h3><p>We found an association between <em>MTHFR</em> rs180133, 677C > T and vitamin B12 status in T2DM patients on metformin therapy. Folic acid, MMA and Hcy were found to have high specificity in concordance with <em>MTHFR</em> which showed to be a good predictor for vitamin B12 deficiency in T2DM patients on metformin therapy.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100938"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100938","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47302970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100910
Iman Niktab , Maryam Haghparast , Mohammad-Hossein Beigi , Timothy L. Megraw , Amirkianoosh Kiani , Kamran Ghaedi
COVID-19 is a newly emerged viral disease that is currently affecting the whole globe. A variety of therapeutic approaches are underway to block the SARS-CoV-2 virus. Among these methods, siRNAs could be a safe and specific option, as they have been tested against other viruses. siRNAs are a class of inhibitor RNAs that act promisingly as mRNA expression blockers and they can be designed to interfere with viral mRNA to block virus replication. In order to do this, we designed and evaluated the efficacy of six highly specific siRNAs, which target essential viral mRNAs with no predicted human genome off-targets. We observed a significant reduction in the copy number viral mRNAs after treatment with the siRNAs, and are expected to inhibit virus replication. We propose siRNAs as a potential co-therapy for acute SARS-CoV-2 infection.
{"title":"Design of advanced siRNA therapeutics for the treatment of COVID-19","authors":"Iman Niktab , Maryam Haghparast , Mohammad-Hossein Beigi , Timothy L. Megraw , Amirkianoosh Kiani , Kamran Ghaedi","doi":"10.1016/j.mgene.2021.100910","DOIUrl":"10.1016/j.mgene.2021.100910","url":null,"abstract":"<div><p>COVID-19 is a newly emerged viral disease that is currently affecting the whole globe. A variety of therapeutic approaches are underway to block the SARS-CoV-2 virus. Among these methods, siRNAs could be a safe and specific option, as they have been tested against other viruses. siRNAs are a class of inhibitor RNAs that act promisingly as mRNA expression blockers and they can be designed to interfere with viral mRNA to block virus replication. In order to do this, we designed and evaluated the efficacy of six highly specific siRNAs, which target essential viral mRNAs with no predicted human genome off-targets. We observed a significant reduction in the copy number viral mRNAs after treatment with the siRNAs, and are expected to inhibit virus replication. We propose siRNAs as a potential co-therapy for acute SARS-CoV-2 infection.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100910"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38906270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-09-01DOI: 10.1016/j.mgene.2021.100926
Shymaa A. Sarhan , Nagwa A. Sherby , Nermin Raafat , Samah M. Alian
Background
Systemic Sclerosis (SSc) is a chronic disease of the connective tissue caused by an autoimmune inflammatory process. Genetic polymorphisms of cytochrome P2D6 (CYP2D6) enzymes have been implicated in the SSc disease etiopathogenesis.
Aim
Our work was designed to investigate the association between the CYP2D6 gene mutation and the risk of SSc development and its relation to different SSc clinical manifestations.
Methods
One hundred SSc patients were involved in the study and one hundred healthy individuals were included to serve as a contol group.
CYP2D6 *1, CYP2D6 *3, CYP2D6 *4 allelic frequencies were analyzed by the Polymerase Chain Reaction- Fragment Length Polymorphism (PCR-RFLP) method.
Results
The heterozygous extensive metabolizers (CYP2D6 *1/*4) genotype showed a statistically significant risk for developing SSc, assessed by the odds ratio (OR = 2.4, P = 0.003). The homozygous extensive metabolizers (CYP2D6 *1/*1) which are the wild genotypes, were expressed less frequently in SSc patients with a significant difference (OR = 0.23) in comparison with the control group. As for the alleles frequency, a significant increase in the risk of SSc was associated with the mutant CYP2D6 *4 allele frequency (OR = 2.2), indicating that the presence of allele CYP2D6*4 is a risky genetic factor for SSc. Diffuse type systemic sclerosis, gastrointestinal (GIT), cardiac, pulmonary manifestations, positive anti-scleroderma 70, moderate restriction in pulmonary function tests, and abnormal Echocardiographic findings were significantly associated with the (CYP2D6 *1/*4) genotype.
Conclusion
Finding of the study revealed a higher prevalence of the heterozygotes extensive metabolizers (CYP2D6 *1/*4)genotypes and the mutant alleles (CYP2D6*4) in SSc patients, suggesting the high impact of the CYP2D6 gene mutation on the SSc development.
{"title":"Association of cytochrome P2D6 gene polymorphism with the susceptibility of Egyptian patients to systemic sclerosis disease","authors":"Shymaa A. Sarhan , Nagwa A. Sherby , Nermin Raafat , Samah M. Alian","doi":"10.1016/j.mgene.2021.100926","DOIUrl":"10.1016/j.mgene.2021.100926","url":null,"abstract":"<div><h3>Background</h3><p>Systemic Sclerosis (SSc) is a chronic disease of the connective tissue caused by an autoimmune inflammatory process. Genetic polymorphisms of cytochrome P2D6 (CYP2D6) enzymes have been implicated in the SSc disease etiopathogenesis.</p></div><div><h3>Aim</h3><p>Our work was designed to investigate the association between the CYP2D6 gene mutation and the risk of SSc development and its relation to different SSc clinical manifestations.</p></div><div><h3>Methods</h3><p>One hundred SSc patients were involved in the study and one hundred healthy individuals were included to serve as a contol group.</p><p>CYP2D6 *1, CYP2D6 *3, CYP2D6 *4 allelic frequencies were analyzed by the Polymerase Chain Reaction- Fragment Length Polymorphism (PCR-RFLP) method.</p></div><div><h3>Results</h3><p>The heterozygous extensive metabolizers (CYP2D6 *1/*4) genotype showed a statistically significant risk for developing SSc, assessed by the odds ratio (OR = 2.4, <em>P</em> = 0.003). The homozygous extensive metabolizers (CYP2D6 *1/*1) which are the wild genotypes, were expressed less frequently in SSc patients with a significant difference <strong>(OR = 0.23)</strong> in comparison with the control group. As for the alleles frequency, a significant increase in the risk of SSc was associated with the mutant CYP2D6 *4 allele frequency (OR = 2.2), indicating that the presence of allele CYP2D6*4 is a risky genetic factor for SSc. Diffuse type systemic sclerosis, gastrointestinal (GIT), cardiac, pulmonary manifestations, positive anti-scleroderma 70, moderate restriction in pulmonary function tests, and abnormal Echocardiographic findings were significantly associated with the (CYP2D6 *1/*4) genotype.</p></div><div><h3>Conclusion</h3><p>Finding of the study revealed a higher prevalence of the heterozygotes extensive metabolizers (CYP2D6 *1/*4)genotypes and the mutant alleles (CYP2D6*4) in SSc patients, suggesting the high impact of the CYP2D6 gene mutation on the SSc development.</p></div>","PeriodicalId":38190,"journal":{"name":"Meta Gene","volume":"29 ","pages":"Article 100926"},"PeriodicalIF":0.7,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.mgene.2021.100926","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47794668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}