scholarly journals Association of Sex Determining Region Y-Box 17 Gene Polymorphisms and Intracranial Aneurysm: A Case-Control Study and Meta-analysis

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Museung Park ◽  
Yong-Jun Cho ◽  
Jin Sue Jeon
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Gene Polymorphisms ◽  
Meta Analysis ◽  
East Asian ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Unruptured Aneurysms ◽  
Asian Populations

Abstract INTRODUCTION Genome-wide association studies have revealed an association between SRY (Sex Determining Region Y)-box 17 (SOX17) gene and intracranial aneurysm (IA) formation. However, results were mainly derived from European and Japanese populations. We investigated the association between SOX17 gene polymorphisms and IA in a homogeneous Korean population. We performed a meta-analysis to assess these results in East-Asian populations. METHODS This cross-sectional study included 187 age- and sex-matched patients with IA and 372 control subjects. Genetic association analysis was performed in the generalized linear model to identify associations between 4 single nucleotide polymorphisms and IA, including 95 patients with ruptured aneurysms and 92 with unruptured aneurysms. The East-Asian meta-analysis of 5100 IA cases and 7930 control cases was conducted under an inverse variance model. RESULTS Among 4 single nucleotide polymorphisms that passed quality control tests, the minor C allele of rs1072737 was significantly associated with IA (odds ratio 0.69, 95% confidence interval 0.49-0.96, P = .03). None of the 4 single nucleotide polymorphisms showed a significant association between patients with ruptured and unruptured aneurysms. Meta-analysis revealed that G alleles of rs10958409 and rs9298506 were significantly associated with IA in the East-Asian population after removing study heterogeneity (odds ratio 1.11, 95% confidence interval 1.04-1.19, P = .0023 and odds ratio 1.19, 95% confidence interval 1.07-1.32, P = .0016). CONCLUSION Identification of genetic variants located near SOX17 is likely to be clinically significant for IA formation. rs10958409 and rs9298506 may increase risk of IA in East-Asian populations. Our findings may help in the identification of IA pathogenesis.

scholarly journals SUN-711 Association of Single Nucleotide Polymorphisms of CYP11B2, CYP11B1 and CYP17A1 with Primary Aldosteronism in a Multi-Ethnic Malaysian Cohort

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Afifah Azam ◽  
Mohammad Arif Shahar ◽  
Siti Liyana Saud Gany ◽  
Norlela Sukor ◽  
Nor Azmi Kamaruddin ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Primary Aldosteronism ◽  
East Asian ◽  
Genotype Imputation ◽  
Chinese Patients ◽  
Nucleotide Polymorphisms ◽  
Steroidogenic Enzyme ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Increased Risk

Abstract Primary aldosteronism (PA), also known as Conn’s syndrome, is a common curable cause of hypertension. Family studies of essential hypertensive patients suggest that heritable genetic factors play a role in blood pressure regulation1. Interestingly, single nucleotide polymorphisms (SNP) in genes encoding enzymes involved with adrenal steroidogenesis, CYP11B2, CYP11B1 and CYP17A1, associate with increased risk of hypertension2. Therefore, we analysed whether selected SNPs in these genes are associated with PA. We performed an association study using genotype imputation for selected SNPs of the steroidogenic enzyme genes CYP11B2 (rs4546, rs1799998, rs13268025), CYP11B1 (rs6410, rs149845727), and CYP17A1 (rs1004467, rs138009835, rs2150927) from a pilot genome wide association study of Malaysian PA patients and healthy controls which was merged with the Singapore Genome Variation Project (SGVP) population dataset3. Genotype imputation for minor and major alleles was validated using PCR sequencing (n>10 for each genotype). Further, one SNP from each steroidogenic enzyme (CYP11B2:rs1799998, CYP11B1:rs6410 and CYP17A1:rs1004467) was validated using commercial TaqMan genotyping assays on the ABI 7000 Sequence Detection System which was performed on 149 PA patients and 78 non-hypertensive healthy individuals. Case-control genetic association analysis was performed at http://www.oege.org/software/orcalc.html and the association between genotypes and phenotypes was done using the independent-samples Kruskal-Wallis test on SPSS (version 25). The Minor Allele Frequencies (MAFs) for rs1004467, rs6410 and rs1799998 were similar to East Asian populations but differed significantly different from European, African, American and South Asian populations (rs1004467 MAF: C=0.258/298, rs6410 MAF: A=0.265/298, rs1799998 MAF: C=0.225/298). In Chinese patients matched by gender, heterozygotes for rs6410 had significantly increased risk of PA compared to common homozygotes (OR: 3.15, 95% CI: 1.01–9.8, p=0.04). Across patients of different ethnicity, the distribution of aldosterone levels was significantly different (p=0.039). In summary, only SNP rs6410 in Chinese patients matched by gender showed association with PA in our South East Asian cohort. More functional experiments need to be done to find out whether this is causal for PA or whether the SNP is in linkage disequilibrium with the actual functional causative SNPs. Once the functional SNP is known, identification of these germline variants in asymptomatic family members would allow early screening of PA to be offered and potentially provide novel drug targets to treat the disease. References: 1Timberlake et al., Curr Opin Nephrol Hypertens. 2001 Jan;10(1):71-9. 2MacKenzie et al., Int J Mol Sci. 2017 Mar 7;18(3). pii: E579. 3Teo et al., Genome Res. 2009 Nov;19(11):2154-62.

scholarly journals Coagulation Factors and the Risk of Ischemic Heart Disease

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie V. Zhao ◽  
C. Mary Schooling
Keyword(s):  
Heart Disease ◽  
Single Nucleotide Polymorphisms ◽  
Confidence Interval ◽  
Ischemic Heart Disease ◽  
Plasminogen Activator ◽  
Odds Ratio ◽  
Coagulation Factors ◽  
Ischemic Heart ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Background: Coagulation plays a role in ischemic heart disease (IHD). However, which coagulation factors are targets of intervention is unclear. We assessed how genetically predicted vWF (von Willebrand factor), ETP (endogenous thrombin potential), FVIII (factor VIII), d -dimer, tPA (tissue-type plasminogen activator), and PAI (plasminogen activator inhibitor)-1 affected IHD. We similarly estimated effects on lipids to determine whether any associations were independent of lipids. Methods and Results: Separate sample instrumental variable analysis with genetic instruments, that is, Mendelian randomization, was used to obtain unconfounded estimates of effects on IHD using extensively genotyped studies of coronary artery disease/myocardial infarction, CARDIoGRAMplusC4D Metabochip (64 374 cases, 130 681 controls) and CARDIoGRAMplusC4D 1000 Genomes (60 801 cases, 123 504 controls), and on lipids using the Global Lipids Genetics Consortium Results (n=196 475). Genetically predicted ETP was positively associated with IHD (odds ratio, 1.05 per log-transformed SD; 95% confidence interval, 1.03–1.07) based on 15 single-nucleotide polymorphisms, as were vWF (odds ratio, 1.05 per SD; 95% confidence interval, 1.02–1.08) and FVIII (odds ratio, 1.06 per SD; 95% confidence interval, 1.03–1.09) based on 16 and 6 single-nucleotide polymorphisms, respectively, but the latter associations were null after considering pleiotropy. vWF and FVIII were associated with higher LDL (low-density lipoprotein) cholesterol, but not after considering pleiotropy. Genetically predicted d -dimer, tPA, and PAI-1 were not clearly associated with IHD or lipids based on 3, 3, and 5 single-nucleotide polymorphisms, respectively. Conclusions: ETP may affect IHD. Assessing the role of its drivers in more precisely phenotyped studies of IHD could be worthwhile.

scholarly journals The Effect of Single Nucleotide Polymorphisms on Depression in Combination With Coronary Diseases: Protocol for a Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
De Zhao Kong ◽  
Lu Gao ◽  
Hang Li ◽  
Yu Wang ◽  
Miao Miao Wang ◽  
...  
Keyword(s):  
Systematic Review ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Single Nucleotide Polymorphisms ◽  
Confidence Interval ◽  
Meta Analysis ◽  
Case Control ◽  
Current Evidence ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

Abstract Background: Depression and coronary heart disease (CHD) have common risk mechanisms. Common single nucleotide polymorphisms (SNPs) may be associated with the risk of depression combined with coronary heart disease. Methods: This protocol was designed according to the PRISMA-P guidelines. CENTRAL in the Cochrane Library, MEDLINE Ovid, Embase Ovid, Web of Science, CNKI, CQVIP, SinoMed, Wanfang Data, and ChiCTR will be systematically searched. We will include case-control studies and cohort studies investigating the relationship between gene SNPs and depression and coronary heart disease comorbidities. The Newcastle-Ottawa Scale (NOS) will be used to assess the risk of bias. When measuring dichotomous outcomes, we will use the risk ratio (RR) and 95% confidence interval (95%CIs) in a cohort study and use the odds ratio (OR) and 95% confidence interval (95%CIs) in a case-control study. Five genetic models (allele model, homozygous model, heterozygous model, dominant model, and recessive model) will be evaluated for each included study. Subgroup analysis by ethnicity will be performed. If necessary, post hoc analysis will be made according to different types.Discussion: The purpose of this meta-analysis is to comprehensively study the current evidence and assess the association between single nucleotide polymorphisms and susceptibility of depression in combination with coronary heart disease.Systematic review registration: This protocol was prospectively registered in the PROSPERO (registration number CRD42021229371).

scholarly journals TMEM41B is a pan-flavivirus host factor

2020 ◽  
Author(s):  
H.-Heinrich Hoffmann ◽  
William M Schneider ◽  
Kathryn Rozen-Gagnon ◽  
Linde A Miles ◽  
Felix Schuster ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
East Asian ◽  
Rna Replication ◽  
Membrane Curvature ◽  
Genome Replication ◽  
Nucleotide Polymorphisms ◽  
Mechanistic Studies ◽  
Single Nucleotide ◽  
Asian Populations ◽  
Flavivirus Infection

SUMMARYFlaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection. Based on our mechanistic studies we hypothesize that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication.HIGHLIGHTSTMEM41B and VMP1 are required for both autophagy and flavivirus infection, however, autophagy is not required for flavivirus infection.TMEM41B associates with viral proteins and likely facilitates membrane remodeling to establish viral RNA replication complexes.TMEM41B single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection.TMEM41B-deficient cells display an exaggerated innate immune response upon high multiplicity flavivirus infection.

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