Meta Gene最新文献

{"title":"Association of reelin gene (RELN) polymorphism with autism spectrum disorder in the Bangladeshi population","authors":"Shahriar Ahmed ,&nbsp;Ahmed Rakib ,&nbsp;Mir Muhammad Nasir Uddin ,&nbsp;Mohammad Safiqul Islam ,&nbsp;S.M. Amanat Ullah ,&nbsp;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 &gt; C and g.504742G &gt; 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 &gt; C and g.504742G &gt; A showed no significant relationship with ASD (χ² = 0.603; <em>p</em> = 0.479 and χ² = 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}

{"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 ,&nbsp;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&gt;T single-nucleotide polymorphism (SNP) and susceptibility to various tumors. However, limited studies have examined the association of DNMT3B 579G&gt;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&gt;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&gt;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}

{"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 ,&nbsp;Nachimuthu Senthil Kumar ,&nbsp;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}

{"title":"Association of the NOTCH4 gene polymorphism with schizophrenia in the Indian population","authors":"Kiran Kumar PVSN ,&nbsp;Prasenjit Mitra ,&nbsp;Raghumoy Ghosh ,&nbsp;SaiKiran Gangam ,&nbsp;Shailja Sharma ,&nbsp;Naresh Nebhinani ,&nbsp;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 &amp; 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 &amp; 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}

{"title":"Influence of IL28B gene polymorphisms on PegINF-RBV-mediated HCV clearance in HIV-HCV co-infected patients: A meta-analysis","authors":"Nirmal Kumar ,&nbsp;Suchitra S. Prabhu ,&nbsp;Isha Monga ,&nbsp;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> &lt; 0.0001; rs8099917, OR = 3.6`9 [95% CI (2.74, 4.97)]; <em>P</em> &lt; 0.0001; rs12980275, OR = 2.97 [95% CI (2.26, 3.89)]; <em>P</em> &lt; 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> &lt; 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}

{"title":"Role of Fok I VDR polymorphism in TB risk assessment; A Study in Central India population","authors":"M. Tiwari ,&nbsp;M.K. Verma ,&nbsp;P.K. Singh ,&nbsp;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}

{"title":"Leu72Met polymorphism of GHRL gene increase the risk factor of obesity in a Javanese ethnic group from Indonesia","authors":"Demes Chornelia Martantiningtyas ,&nbsp;Pramudji Hastuti ,&nbsp;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> &lt; 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}

{"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 ,&nbsp;Ramesh Ramasamy ,&nbsp;M. Lenin ,&nbsp;Kuzhandai Velu ,&nbsp;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> &lt; 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 &gt; 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}

{"title":"Design of advanced siRNA therapeutics for the treatment of COVID-19","authors":"Iman Niktab ,&nbsp;Maryam Haghparast ,&nbsp;Mohammad-Hossein Beigi ,&nbsp;Timothy L. Megraw ,&nbsp;Amirkianoosh Kiani ,&nbsp;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}

{"title":"Association of cytochrome P2D6 gene polymorphism with the susceptibility of Egyptian patients to systemic sclerosis disease","authors":"Shymaa A. Sarhan ,&nbsp;Nagwa A. Sherby ,&nbsp;Nermin Raafat ,&nbsp;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}