Pub Date : 2024-06-01Epub Date: 2024-05-08DOI: 10.1089/gtmb.2023.0690
Yaneris Maibeth Romero-Bolaño, Lucina Bobadilla-Morales, Alfredo Corona-Rivera, Idalid Cuero-Quezada, Jennifer Santana-Hernández, Christian Peña-Padilla, Alejandro Brukman-Jiménez, Mireya Orozco-Vela, Natalia Navia-Espinoza, Jorge Román Corona-Rivera
Background: Several studies in mothers of infants with Down syndrome (DS) (MoIDS) have suggested that the 677C>T and 1298A>C variants of the 5,10-methylentetrahydrofolate reductase (MTHFR) gene can increase the risk of having a child with DS. Aim: This study aimed to evaluate the MTHFR 677C>T and 1298A>C variants as potential maternal risk factors for DS. Materials and Methods: Using TaqMan allelic discrimination assay, we genotyped 95 MoIDS and 164 control mothers from western Mexico. Data were analyzed using logistic regression analysis. Results: We found that MoIDS had a significantly higher risk for the MTHFR 677TT genotype (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.1-10.6), and the MTHFR 677T allele (aOR = 1.5, 95% CI: 1.0-2.3), particularly in MoIDS <35 years of age. Conclusions: Our findings indicate that the presence of the 677TT genotype and 677T allele of the MTHFR 677C>T variant are maternal risk factors for DS in Mexican MoIDS.
{"title":"<i>MTHFR</i> 677C>T and 1298A>C Variants in Mothers of Infants with Down Syndrome from Western Mexico.","authors":"Yaneris Maibeth Romero-Bolaño, Lucina Bobadilla-Morales, Alfredo Corona-Rivera, Idalid Cuero-Quezada, Jennifer Santana-Hernández, Christian Peña-Padilla, Alejandro Brukman-Jiménez, Mireya Orozco-Vela, Natalia Navia-Espinoza, Jorge Román Corona-Rivera","doi":"10.1089/gtmb.2023.0690","DOIUrl":"10.1089/gtmb.2023.0690","url":null,"abstract":"<p><p><b><i>Background:</i></b> Several studies in mothers of infants with Down syndrome (DS) (MoIDS) have suggested that the 677C>T and 1298A>C variants of the 5,10-methylentetrahydrofolate reductase (<i>MTHFR</i>) gene can increase the risk of having a child with DS. <b><i>Aim:</i></b> This study aimed to evaluate the <i>MTHFR</i> 677C>T and 1298A>C variants as potential maternal risk factors for DS. <b><i>Materials and Methods:</i></b> Using TaqMan allelic discrimination assay, we genotyped 95 MoIDS and 164 control mothers from western Mexico. Data were analyzed using logistic regression analysis. <b><i>Results:</i></b> We found that MoIDS had a significantly higher risk for the <i>MTHFR</i> 677TT genotype (adjusted odds ratio [aOR] = 3.4, 95% confidence interval [95% CI]: 1.1-10.6), and the <i>MTHFR</i> 677T allele (aOR = 1.5, 95% CI: 1.0-2.3), particularly in MoIDS <35 years of age. <b><i>Conclusions:</i></b> Our findings indicate that the presence of the 677TT genotype and 677T allele of the <i>MTHFR</i> 677C>T variant are maternal risk factors for DS in Mexican MoIDS.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aims: Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the NLRP3 gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. Materials and Methods: The regulatory single nuclear polymorphisms (SNPs) located in NLRP3 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of NLRP3 and the expression level of inflammatory factors downstream of NLRP3 were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. Results: The study included 418 participants (249 in the COPD group and 169 in the control group). NLRP3 SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (p = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (p < 0.05). Except for rs10754558, all homozygous mutants increased NLRP3 mRNA and protein levels. NLRP3 had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). Conclusions: The NLRP3 rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The NLRP3 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in NLRP3 expression. In the development of COPD, NLRP3 has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.
{"title":"The 3'UTR Polymorphisms in the <i>NLRP3</i> Gene Associated with the Risk of COPD and Their Putative Effects on the microRNA Mechanism.","authors":"Huiyan Wu, Chuting Huang, Yanling Zhang, Xin Yang, Liang Peng, Weipeng Li","doi":"10.1089/gtmb.2023.0229","DOIUrl":"10.1089/gtmb.2023.0229","url":null,"abstract":"<p><p><b><i>Aims:</i></b> Evaluating the association between a single nucleotide polymorphism in the 3' untranslated region (3'UTR) of the miRNA binding site of the <i>NLRP3</i> gene and the occurrence and development of chronic obstructive pulmonary disease (COPD) and providing information to aid in the early detection and treatment of COPD. <b><i>Materials and Methods:</i></b> The regulatory single nuclear polymorphisms (SNPs) located in <i>NLRP3</i> 3'UTR were searched by using the dbSNP database and miRNA binding site prediction database. Meanwhile, samples from COPD patients and healthy controls in the same period were used for verification. The clinical baseline information of all subjects was collected, and the transcription level and protein expression level of <i>NLRP3</i> and the expression level of inflammatory factors downstream of <i>NLRP3</i> were detected. The effects of SNPs' single nucleotide changes on the transcription and expression of inflammatory factors were analyzed. <b><i>Results:</i></b> The study included 418 participants (249 in the COPD group and 169 in the control group). <i>NLRP3</i> SNPs with miRNA binding sites include rs10754558 (G > C), rs1664774076 (ATAT > del), and rs1664775106 (C > G). Furthermore, two genotypes, GCG and GCA, were discovered to have a linkage mutation at 3'UTR 459-461. COPD susceptibility is tightly associated with the expression of the rs1664774076 del/del genotype, and the risk of COPD increased by 2.770 times (<i>p</i> = 0.003). Type 459-461 GCA was substantially related to the likelihood of developing COPD at various stages (<i>p</i> < 0.05). Except for rs10754558, all homozygous mutants increased <i>NLRP3</i> mRNA and protein levels. <i>NLRP3</i> had the greatest area under the receiver operating characteristic (ROC) curve for predicting the development and diagnosis of COPD when compared with its downstream inflammatory variables (AUC = 0.9291). <b><i>Conclusions:</i></b> The <i>NLRP3</i> rs1664774076 del/del genotype is a COPD susceptibility gene, and the GCA genotype at 459-461 can be used as an early predictor of COPD exacerbation. The <i>NLRP3</i> 3'UTR polymorphism may alter the loss of miRNA binding sites, leading to an increase in <i>NLRP3</i> expression. In the development of COPD, <i>NLRP3</i> has a better diagnostic value than traditional inflammatory factors. The Clinical Trials Registration number Z: protocol KY01-2020-11-06.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140957082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular life-threatening disorder. Owing to high carrier frequency, population-wide SMA screening to quantify the copy number of SMN gene is recommended by American College of Medical Genetics and Genomics. An accurate, reliable, short runaround time and cost-effective method may be helpful in mass population screening for SMA. Methods: Multiplex ligation-dependent probe amplification (MLPA) is a gold standard to estimate the copy number variation (CNV) for SMN1 and SMN2 genes. In this study, we validated droplet digital polymerase chain reaction (ddPCR) for the determination of CNV for both SMN1 and SMN2 exon 7 for a diagnostic purpose. In total, 66 clinical samples were tested using ddPCR, and results were compared with the MLPA as a reference test. Results: For all samples, CNV for SMN1 and SMN2 exon 7 was consentaneous between ddPCR and MLPA test results (κ = 1.000, p < 0.0001). In addition, ddPCR also showed a significant acceptable degree of test repeatability, coefficient of variation < 4%. Conclusion: ddPCR is expected to be utilitarian for CNV detection for carrier screening and diagnosis of SMA. ddPCR test results for CNV detection for SMN1/SMN2 exon 7 are concordant with the gold standard. ddPCR is a more cost-effective and time-saving diagnostic test for SMA than MLPA. Furthermore, it can be used for population-wide carrier screening for SMA.
{"title":"Carrier Screening and Diagnosis for Spinal Muscular Atrophy Using Droplet Digital PCR Versus MLPA: Analytical Validation and Early Test Outcome.","authors":"Dolat Singh Shekhawat, Siyaram Didel, Shilpi Gupta Dixit, Pratibha Singh, Kuldeep Singh","doi":"10.1089/gtmb.2023.0073","DOIUrl":"10.1089/gtmb.2023.0073","url":null,"abstract":"<p><p><b><i>Background:</i></b> Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular life-threatening disorder. Owing to high carrier frequency, population-wide SMA screening to quantify the copy number of <i>SMN</i> gene is recommended by American College of Medical Genetics and Genomics. An accurate, reliable, short runaround time and cost-effective method may be helpful in mass population screening for SMA. <b><i>Methods:</i></b> Multiplex ligation-dependent probe amplification (MLPA) is a gold standard to estimate the copy number variation (CNV) for <i>SMN1</i> and <i>SMN2</i> genes. In this study, we validated droplet digital polymerase chain reaction (ddPCR) for the determination of CNV for both <i>SMN1</i> and <i>SMN2</i> exon 7 for a diagnostic purpose. In total, 66 clinical samples were tested using ddPCR, and results were compared with the MLPA as a reference test. <b><i>Results:</i></b> For all samples, CNV for <i>SMN1</i> and <i>SMN2</i> exon 7 was consentaneous between ddPCR and MLPA test results (κ = 1.000, <i>p</i> < 0.0001). In addition, ddPCR also showed a significant acceptable degree of test repeatability, coefficient of variation < 4%. <b><i>Conclusion:</i></b> ddPCR is expected to be utilitarian for CNV detection for carrier screening and diagnosis of SMA. ddPCR test results for CNV detection for <i>SMN1</i>/<i>SMN2</i> exon 7 are concordant with the gold standard. ddPCR is a more cost-effective and time-saving diagnostic test for SMA than MLPA. Furthermore, it can be used for population-wide carrier screening for SMA.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: We aim to investigate the possible causal association between Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) using Mendelian randomization (MR) methods. Methods: A bidirectional MR analysis was conducted to evaluate the causal association between HT and RA. We obtained summary statistics data from two extensive genome-wide association studies (GWAS) comprising 15,654 cases of HT and 14,361 cases of RA. The primary effect estimate utilized in this study was the inverse-variance weighted (IVW) method. To ensure the reliability and stability of the results, we employed several additional methods for testing, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results: Our study revealed compelling evidence of bidirectional causality between HT and RA. When HT was considered as an exposure factor and RA was considered as an outcome factor, this study revealed a positive correlation between HT and RA (IVW: odds ratio [OR] = 2.4546, 95% confidence interval [CI], 1.1473-5.2512; p = 0.0207). Conversely, when we examined RA as the exposure factor and HT as the outcome factor, we still found a positive correlation between them (IVW: OR = 1.2113, 95% CI, 1.1248-1.3044; p = 3.9478 × 10-7). Conclusions: According to our research findings, there exists a bidirectional positive causal relationship between HT and RA among European populations. This implies that individuals with HT have an elevated risk of developing RA, and conversely, individuals with RA have an increased risk of developing HT.
背景:我们旨在利用孟德尔随机化(MR)方法研究桥本氏甲状腺炎(HT)与类风湿性关节炎(RA)之间可能存在的因果关系。研究方法为评估桥本氏甲状腺炎与类风湿关节炎之间的因果关系,我们进行了双向 MR 分析。我们从两项广泛的全基因组关联研究(GWAS)中获得了汇总统计数据,其中包括 15654 例 HT 和 14361 例 RA。本研究采用的主要效应估计方法是逆方差加权法(IVW)。为确保结果的可靠性和稳定性,我们还采用了其他几种方法进行测试,包括 MR-Egger、加权中位数、简单模式、加权模式和 MR-PRESSO。结果我们的研究揭示了 HT 与 RA 之间双向因果关系的有力证据。当 HT 被视为暴露因素,而 RA 被视为结果因素时,本研究显示 HT 与 RA 之间存在正相关性(IVW:几率比 [OR] = 2.4546,95% 置信区间 [CI],1.1473-5.2512;P = 0.0207)。相反,当我们将 RA 作为暴露因素,将 HT 作为结果因素时,我们仍然发现它们之间存在正相关性(IVW:OR = 1.2113,95% 置信区间 [CI],1.1248-1.3044;P = 3.9478 × 10-7)。结论根据我们的研究结果,在欧洲人群中,高血压与 RA 之间存在双向的正向因果关系。这意味着患有 HT 的人患 RA 的风险会升高,反之,患有 RA 的人患 HT 的风险也会升高。
{"title":"Association Between Hashimoto's Thyroiditis and Rheumatoid Arthritis: A Bidirectional Mendelian Randomization Study.","authors":"Jialin Liang, Zhaopu Jing, Yuanqing Cai, Leifeng Lv, Guangyang Zhang, Kai Nan, Xiaoqian Dang","doi":"10.1089/gtmb.2023.0594","DOIUrl":"10.1089/gtmb.2023.0594","url":null,"abstract":"<p><p><b><i>Background:</i></b> We aim to investigate the possible causal association between Hashimoto's thyroiditis (HT) and rheumatoid arthritis (RA) using Mendelian randomization (MR) methods. <b><i>Methods:</i></b> A bidirectional MR analysis was conducted to evaluate the causal association between HT and RA. We obtained summary statistics data from two extensive genome-wide association studies (GWAS) comprising 15,654 cases of HT and 14,361 cases of RA. The primary effect estimate utilized in this study was the inverse-variance weighted (IVW) method. To ensure the reliability and stability of the results, we employed several additional methods for testing, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. <b><i>Results:</i></b> Our study revealed compelling evidence of bidirectional causality between HT and RA. When HT was considered as an exposure factor and RA was considered as an outcome factor, this study revealed a positive correlation between HT and RA (IVW: odds ratio [OR] = 2.4546, 95% confidence interval [CI], 1.1473-5.2512; <i>p</i> = 0.0207). Conversely, when we examined RA as the exposure factor and HT as the outcome factor, we still found a positive correlation between them (IVW: OR = 1.2113, 95% CI, 1.1248-1.3044; <i>p</i> = 3.9478 × 10<sup>-7</sup>). <b><i>Conclusions:</i></b> According to our research findings, there exists a bidirectional positive causal relationship between HT and RA among European populations. This implies that individuals with HT have an elevated risk of developing RA, and conversely, individuals with RA have an increased risk of developing HT.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tingting Tang, Jinyu Gao, Xiangyang Pan, Qianqian Tang, H. Long, Zhaohua Liu
Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1β, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.
{"title":"YKL-40 Knockdown Decreases Oxidative Stress Damage in Ovarian Granulosa Cells.","authors":"Tingting Tang, Jinyu Gao, Xiangyang Pan, Qianqian Tang, H. Long, Zhaohua Liu","doi":"10.1089/gtmb.2023.0361","DOIUrl":"https://doi.org/10.1089/gtmb.2023.0361","url":null,"abstract":"Background: Oxidative stress has been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). To develop novel antioxidant drugs, it is necessary to explore the key regulatory molecules involved in oxidative stress in PCOS. Plasma YKL-40 levels are elevated in patients with PCOS; however, its role remains unclear. Methods: The follicular fluids of 20 women with PCOS and 12 control subjects with normal ovarian function were collected, and YKL-40 in follicular fluids was measured by enzyme-linked immunosorbent assay. A letrozole-induced PCOS rat model was established and the expression level of YKL-40 in the ovaries was detected by immunohistochemistry. KGN cells were treated with H2O2 to generate an ovarian granulosa cell (OGC) model of oxidative stress. The siRNA was transfected into the cells for knockdown. The effect of YKL-40 knockdown on H2O2-treated KGN cells was evaluated by measuring proliferation, apoptosis, activities of T-SOD, GSH-Px, and CAT, levels of MDA, IL-1β, IL-6, IL-8, and TNF-α, and the PI3K/AKT/NF-κB signaling pathway. Results: YKL-40 levels were elevated in the follicular fluids of women with PCOS compared with control subjects with normal ovarian function. The expression level of YKL-40 in the ovaries of rats with PCOS is obviously higher than that in the ovaries of the control group rats. H2O2 treatment enhanced YKL-40 mRNA expression and protein secretion. YKL-40 knockdown enhanced cell proliferation and antioxidant capacity while decreasing apoptosis and inflammatory factor levels in KGN cells following H2O2 treatment. The knockdown activated the PI3K/AKT signaling pathway and suppressed NF-κB nuclear translocation from the cytoplasm. Conclusion: YKL-40 levels were elevated in the follicular fluids of women with PCOS and the ovaries of rats with PCOS. YKL-40 expression can be induced by oxidative stress, and YKL-40 knockdown can decrease oxidative stress damage in OGCs.","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140688576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.
{"title":"Association Study of Pleural Mesothelioma and Oncogenic Simian Virus 40 in the Crocidolite-Contaminated Area of Dayao County, Yunnan Province, Southwest China.","authors":"Ru-Ai Liu, Bo-Yong Wang, Xin Chen, Yuan-Qian Pu, Jia-Ji Zi, Wen Mei, Ye-Pin Zhang, Lu Qiu, Wei Xiong","doi":"10.1089/gtmb.2023.0532","DOIUrl":"https://doi.org/10.1089/gtmb.2023.0532","url":null,"abstract":"Background: In Dayao County, Chuxiong Yi Autonomous Prefecture, Yunnan Province, Southwest China, 5% of the surface is scattered with blue asbestos, which has a high incidence of pleural mesothelioma (PMe). Simian virus 40 (SV40) is a small circular double-stranded DNA polyomavirus that can cause malignant transformation of normal cells of various human and animal tissue types and promote tumor growth. In this study, we investigate whether oncogenic SV40 is associated with the occurrence of PMe in the crocidolite-contaminated area of Dayao County, Yunnan Province, Southwest China. Methods: Tumor tissues from 51 patients with PMe (40 of whom had a history of asbestos exposure) and pleural tissues from 12 non-PMe patients (including diseases such as pulmonary maculopathy and pulmonary tuberculosis) were collected. Three pairs of low-contamination risk primers (SVINT, SVfor2, and SVTA1) were used to detect the gene fragment of SV40 large T antigen (T-Ag) by polymerase chain reaction (PCR). The presence of SV40 T-Ag in PMe tumor tissues and PMe cell lines was detected by Western blotting and immunohistochemical staining with SV40-related antibodies (PAb 101 and PAb 416). Results: PCR, Western blotting, and immunohistochemical staining results showed that the Met5A cell line was positive for SV40 and contained the SV40 T-Ag gene and protein. In contrast, the various PMe cell lines NCI-H28, NCI-H2052, and NCI-H2452 were negative for SV40. PCR was negative for all three sets of low-contamination risk primers in 12 non-PMe tissues and 51 PMe tissues. SV40 T-Ag was not detected in 12 non-PMe tissues or 51 PMe tissues by immunohistochemical staining. Conclusion: Our data suggest that the occurrence of PMe in the crocidolite-contaminated area of Yunnan Province may not be related to SV40 infection and that crocidolite exposure may be the main cause of PMe. The Clinical Trial Registration number: 2020-YXLL20.","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140687868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
DeSanto-Shinawi syndrome (DESSH, OMIM #616708) is a rare genetic disorder caused by pathogenic variants in the WAC gene. This syndrome is characterized by a wide range of physical and neurological symptoms including dysmorphic features, developmental delay, intellectual disability, and behavioral abnormalities. DESSH was described by DeSanto in 2015, and since then, only a few dozen cases have been reported worldwide. Recent research has focused on identifying the underlying genetic cause of the syndrome as well as exploring potential treatments. In this report, we describe a female case who had dysmorphic features including long palpebral fissures, depressed nasal root, mild bulbous nasal tip, thin upper lip, hypertrichosis, short fingers, and intellectual disability, speech delay, and motor retardation. In addition, she had behavioral abnormalities such as agitation, anxiety, and attention deficit hyperactivity disorder (ADHD). Clinical exome sequencing showed a pathogenic heterozygous nonsense variant in exon 13 of the WAC gene c.1837C>T, p.(Arg613Ter) with de novo inheritance. To the best of our knowledge, this is the first case of DESSH reported from Turkey. We aimed to report this rare syndrome and compare the clinical findings of our case with previously reported cases in the literature.
{"title":"The Phenotypic Spectrum of Desanto-Shinawi Syndrome: A Comparative Report of the First Reported Case in Turkey.","authors":"Cisem Mail, S. Yalçıntepe, D. Eker, H. Gurkan","doi":"10.1089/gtmb.2023.0285","DOIUrl":"https://doi.org/10.1089/gtmb.2023.0285","url":null,"abstract":"DeSanto-Shinawi syndrome (DESSH, OMIM #616708) is a rare genetic disorder caused by pathogenic variants in the WAC gene. This syndrome is characterized by a wide range of physical and neurological symptoms including dysmorphic features, developmental delay, intellectual disability, and behavioral abnormalities. DESSH was described by DeSanto in 2015, and since then, only a few dozen cases have been reported worldwide. Recent research has focused on identifying the underlying genetic cause of the syndrome as well as exploring potential treatments. In this report, we describe a female case who had dysmorphic features including long palpebral fissures, depressed nasal root, mild bulbous nasal tip, thin upper lip, hypertrichosis, short fingers, and intellectual disability, speech delay, and motor retardation. In addition, she had behavioral abnormalities such as agitation, anxiety, and attention deficit hyperactivity disorder (ADHD). Clinical exome sequencing showed a pathogenic heterozygous nonsense variant in exon 13 of the WAC gene c.1837C>T, p.(Arg613Ter) with de novo inheritance. To the best of our knowledge, this is the first case of DESSH reported from Turkey. We aimed to report this rare syndrome and compare the clinical findings of our case with previously reported cases in the literature.","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140708046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deepanshi Mahajan, V. Sambyal, M. Uppal, M. Sudan, K. Guleria
Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF-2578C/A and VEGF-460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF-2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF-460T/C polymorphism were genotyped. AA genotype (p = 0.01) and A allele (p = 0.02) of VEGF-2578C/A and CC genotype (p = 0.04) and C allele (p = 0.04) of VEGF-460T/C polymorphism were significantly associated with an increased risk of EC. VEGF-2578C/A and VEGF-460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF-2578C/A and 20 studies on VEGF-460T/C polymorphism were included in this meta-analysis. VEGF-2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model (p = 0.009). A significant association of VEGF-2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF-460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF-2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF-460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF-2578C/A and VEGF-460T/C polymorphisms were associated with GIT cancer risk.
{"title":"VEGF-2578C/A, -460T/C Polymorphisms and Gastrointestinal Tract Cancer Risk: An Updated Meta-Analysis.","authors":"Deepanshi Mahajan, V. Sambyal, M. Uppal, M. Sudan, K. Guleria","doi":"10.1089/gtmb.2023.0628","DOIUrl":"https://doi.org/10.1089/gtmb.2023.0628","url":null,"abstract":"Functional polymorphisms in the vascular endothelial growth factor (VEGF) alter the susceptibility toward different gastrointestinal tract (GIT) cancers. In this study, we explored the association of VEGF-2578C/A and VEGF-460T/C polymorphisms with esophageal cancer (EC) risk. In total, 330 patients with EC and 330 controls for VEGF-2578C/A polymorphism and 316 patients with EC and 316 controls for VEGF-460T/C polymorphism were genotyped. AA genotype (p = 0.01) and A allele (p = 0.02) of VEGF-2578C/A and CC genotype (p = 0.04) and C allele (p = 0.04) of VEGF-460T/C polymorphism were significantly associated with an increased risk of EC. VEGF-2578C/A and VEGF-460T/C polymorphisms have been studied in different GIT cancers, but results are inconclusive. Therefore, we performed a meta-analysis to assess the association of these polymorphisms with the risk of GIT cancers. The PubMed, ScienceDirect, and Google Scholar databases were used to search the articles. Twenty-one studies on VEGF-2578C/A and 20 studies on VEGF-460T/C polymorphism were included in this meta-analysis. VEGF-2578C/A polymorphism was associated with the decreased risk of GIT cancer in the overall population under the overdominant model (p = 0.009). A significant association of VEGF-2578C/A polymorphism with GIT cancer risk has been observed in the middle easterners, Caucasians, and Asians under different genetic models. VEGF-460T/C polymorphism was significantly associated with an increased risk of GIT cancers in Caucasians. Stratification of the data on the basis of cancer type showed a significant association of VEGF-2578C/A polymorphism with the risk of gallbladder cancer, whereas VEGF-460T/C polymorphism was associated with the risk of hepatocellular cancer, gastric cancer, and colorectal cancer. Our meta-analysis suggested that VEGF-2578C/A and VEGF-460T/C polymorphisms were associated with GIT cancer risk.","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140716415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Somayya Naguib, Lamiaa A Mansour, Neveen A. Soliman, Hadeel M El-Hanafy, Y. Fahmy, M. Elmonem, Radwa M Abdel Halim
Introduction: Approximately 80% of primary hyperoxaluria cases are caused by primary hyperoxaluria type 1 (PH1, OMIM# 259900), which is characterized by pathogenic variants in the AGXT gene, resulting in deficiency of the liver-specific enzyme alanine-glyoxylate aminotransferase (AGT). This leads to increased production of oxalate, which cannot be effectively eliminated from the body, resulting in its accumulation primarily in the kidneys and other organs. Subjects and Methods: This study included 17 PH1 Egyptian patients from 12 unrelated families, recruited from the Inherited Kidney Disease Outpatient Clinic and the Dialysis Units, Cairo University Hospitals, during the period from January 2018 to December 2019, aiming to identify the pathogenic variants in the AGXT gene. Results: Six different variants were detected. These included three frameshift and three missense variants, all found in homozygosity within the respective families. The most common variant was c.121G>A;p.(Gly41Arg) detected in four families, followed by c.725dup;p.(Asp243GlyfsTer12) in three families, c.33dup;p.(Lys12Glnfs156) in two families, and c.731T >C;p.(Ile244Thr), c.33delC;p.(Lys12Argfs34), and c.568G>A;p.(Gly190Arg) detected in one family each. Conclusion: Consanguineous Egyptian families with history of renal stones or renal disease suspicious of primary hyperoxaluria should undergo AGXT genetic sequencing, specifically targeting exons 1 and 7, as variants in these two exons account for >75% of disease-causing variants in Egyptian patients with confirmed PH1.
{"title":"Expanding the Genetic Spectrum of AGXT Gene Variants in Egyptian Patients with Primary Hyperoxaluria Type I.","authors":"Somayya Naguib, Lamiaa A Mansour, Neveen A. Soliman, Hadeel M El-Hanafy, Y. Fahmy, M. Elmonem, Radwa M Abdel Halim","doi":"10.1089/gtmb.2023.0525","DOIUrl":"https://doi.org/10.1089/gtmb.2023.0525","url":null,"abstract":"Introduction: Approximately 80% of primary hyperoxaluria cases are caused by primary hyperoxaluria type 1 (PH1, OMIM# 259900), which is characterized by pathogenic variants in the AGXT gene, resulting in deficiency of the liver-specific enzyme alanine-glyoxylate aminotransferase (AGT). This leads to increased production of oxalate, which cannot be effectively eliminated from the body, resulting in its accumulation primarily in the kidneys and other organs. Subjects and Methods: This study included 17 PH1 Egyptian patients from 12 unrelated families, recruited from the Inherited Kidney Disease Outpatient Clinic and the Dialysis Units, Cairo University Hospitals, during the period from January 2018 to December 2019, aiming to identify the pathogenic variants in the AGXT gene. Results: Six different variants were detected. These included three frameshift and three missense variants, all found in homozygosity within the respective families. The most common variant was c.121G>A;p.(Gly41Arg) detected in four families, followed by c.725dup;p.(Asp243GlyfsTer12) in three families, c.33dup;p.(Lys12Glnfs156) in two families, and c.731T >C;p.(Ile244Thr), c.33delC;p.(Lys12Argfs34), and c.568G>A;p.(Gly190Arg) detected in one family each. Conclusion: Consanguineous Egyptian families with history of renal stones or renal disease suspicious of primary hyperoxaluria should undergo AGXT genetic sequencing, specifically targeting exons 1 and 7, as variants in these two exons account for >75% of disease-causing variants in Egyptian patients with confirmed PH1.","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140763309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Micro RNAs are new diagnostic markers and therapeutic targets in breast cancer research. miR-107 and miR-126 have been reported to be linked with the pathogenesis of breast cancer. The present study investigates the levels of expression of miR-107 and miR-126 in patients with breast cancer to find their correlation with the risk of breast cancer in Amritsar, Punjab, Northwest India. Material and Methods: In total, 200 subjects, 100 patients with breast cancer and 100 controls, were enrolled to screen the expression of miR-107 and miR-126 using quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. The Livak method (2-ΔΔCt) was used to calculate the fold change of the expression of micro RNAs. Student t-test was used to calculate the significant change in the expression of miRNAs in patients as compared with controls. Spearman rank correlation coefficient and ROC were conducted. The value of p < 0.05 was considered to indicate a statistically significant difference. Results: miR-107 was downregulated in patients with breast cancer as compared with controls (fold change = 0.467; p = 0.114) but not statistically significant. The expression of miR-126 was found to be 5.37 times elevated in patients with breast cancer, specifically in stage I and stage III patients (p = 0.009), compared with controls, which may indicate its oncogenic activity. The ROC analyses revealed that miR-126 could be a potential diagnostic marker. In conclusion oncogenic behavior of miR-126 is suggestive of its role in pathogenesis in patients with breast cancer.
{"title":"miR-107 and miR-126 and Risk of Breast Cancer: A Case-Control Study.","authors":"Priyanka Gupta, Vasudha Sambyal, Jagmohan Singh Bali, Kamlesh Guleria, Manjit Singh Uppal, Meena Sudan","doi":"10.1089/gtmb.2023.0606","DOIUrl":"10.1089/gtmb.2023.0606","url":null,"abstract":"<p><p><b><i>Background:</i></b> Micro RNAs are new diagnostic markers and therapeutic targets in breast cancer research. miR-107 and miR-126 have been reported to be linked with the pathogenesis of breast cancer. The present study investigates the levels of expression of miR-107 and miR-126 in patients with breast cancer to find their correlation with the risk of breast cancer in Amritsar, Punjab, Northwest India. <b><i>Material and Methods:</i></b> In total, 200 subjects, 100 patients with breast cancer and 100 controls, were enrolled to screen the expression of miR-107 and miR-126 using quantitative reverse transcription polymerase chain reaction (RT-PCR) technique. The Livak method (2<sup>-ΔΔCt</sup>) was used to calculate the fold change of the expression of micro RNAs. Student <i>t</i>-test was used to calculate the significant change in the expression of miRNAs in patients as compared with controls. Spearman rank correlation coefficient and ROC were conducted. The value of <i>p</i> < 0.05 was considered to indicate a statistically significant difference. <b><i>Results:</i></b> miR-107 was downregulated in patients with breast cancer as compared with controls (fold change = 0.467; <i>p</i> = 0.114) but not statistically significant. The expression of miR-126 was found to be 5.37 times elevated in patients with breast cancer, specifically in stage I and stage III patients (<i>p</i> = 0.009), compared with controls, which may indicate its oncogenic activity. The ROC analyses revealed that miR-126 could be a potential diagnostic marker. In conclusion oncogenic behavior of miR-126 is suggestive of its role in pathogenesis in patients with breast cancer.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}