Dataset Information

CYP11B2 T-344C gene polymorphism and atrial fibrillation: a meta-analysis of 2,758 subjects.

ABSTRACT:

Background

Aldosterone synthase (CYP11B2) T-344C gene polymorphism was found to be correlated with atrial fibrillation (AF) risk. However, the results of individual studies remain conflicting.

Objective and methods

A meta-analysis including 2,758 subjects from six individual studies was performed to explore the correlation between CYP11B2 T-344C gene polymorphisms and AF. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by the fixed- or random-effects model.

Results

A significant relationship between CYP11B2 T-344C gene polymorphism and AF was found under allelic (OR: 1.26, 95% CI: 1.11-1.42, P?=?0.0002), recessive (OR: 1.99, 95% CI: 1.26-3.14, P?=?0.003), dominant (OR: 0.903, 95% CI: 0.820-0.994, P?=?0.036), homozygous (OR: 1.356, 95% CI: 1.130-1.628, P?=?0.001), and additive (OR: 1.153, 95% CI: 1.070-1.243, P?=?1.0×10(-10)) genetic models. No significant association between CYP11B2 T-344C gene polymorphism and AF was found under the heterozygous genetic model (OR: 1.040, 95% CI: 0.956-1.131, P?=?0.361).

Conclusions

A significant association was found between CYP11B2 T-344C gene polymorphism and AF risk. Individuals with the C allele of CYP11B2 T-344C gene polymorphism have higher risk for AF.

SUBMITTER: Li YY

PROVIDER: S-EPMC3509071 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

CYP11B2 T-344C gene polymorphism and atrial fibrillation: a meta-analysis of 2,758 subjects.

Li Yan-yan YY Zhou Chuan-wei CW Xu Jian J Qian Yun Y Wang Bei B

PloS one 20121128 11

<h4>Background</h4>Aldosterone synthase (CYP11B2) T-344C gene polymorphism was found to be correlated with atrial fibrillation (AF) risk. However, the results of individual studies remain conflicting.<h4>Objective and methods</h4>A meta-analysis including 2,758 subjects from six individual studies was performed to explore the correlation between CYP11B2 T-344C gene polymorphisms and AF. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs) were evaluated by the ...[more]

PMID: 23209837

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Project description:OBJECTIVE:To investigate the correlation between KCNA5 single nucleotide polymorphism (SNP) and idiopathic atrial fibrillation (IAF). METHODS:A case-control study was conducted, including 282 cases of IAF patients and 300 cases of age and sex-matched normal controls; gene sequencing method was used to detect the distribution of KCNA5 SNP (rs3741930 and rs1056468) in the two groups. The IAF patients were divided into two groups based on the different genotypes of rs1056468 and rs3741930; differences in clinical parameters between the two groups of patients were compared. RESULTS:For rs3741930, the CC, CT and TT genotype frequencies in the IAF group were 16.7%, 50.0%, and 33.3% respectively; C allele frequency in IAF group was 41.7%; in the normal control group, those were 10.0%, 49.3%, 40.7% and 34.7% respectively; CC genotype frequency and C allele frequency in IAF group were significantly higher compared with the control group (P=0.019, P=0.014). For rs1056468, the AA, AT and TT genotype frequencies in the IAF group were 44.3%, 48.6%, and 7.1% respectively; in 300 cases of normal controls, those were 38.7%, 50.7%, and 10.6% respectively; A allele frequency in IAF group was 68.6 %, and it was 64.0% in normal controls. There were no significant differences in genotype and allele frequencies between control and IAF groups (P>0.05). In IAF group, among different genotypes of rs1741930 and rs1056468, there were no significant differences in age, SBP, DBP, HR, LAD and LVEF (P>0.05). While the BMI in CC and CC+TT groups of rs3741930 locus were 26.9±2.3 Kg/m(2) and 24.8±2.5 Kg/m(2) respectively. There were statistical differences between the two groups (P=0.019). BMI in AA and AA+TT groups of rs1056468 locus were 24.9±2.7 Kg/m(2) and 26.4±2.4 Kg/m(2) respectively; There was statistically significant significance between the two groups (P=0.014). CONCLUSION:The single nucleotide polymorphism rs3741930 locus in KCNA5 gene was related to the risk of IAF; the population carrying C allele was more susceptible to IAF; the polymorphic loci, rs3741930 and rs1056468, were correlated with the BMI of IAF patients.

Project description:The atrial gap junction protein connexin-40 (Cx40) has been implicated to play an important role in atrial conduction and development of atrial fibrillation (AF). However, the frequency of Cx40 mutations in AF populations and their impact on Cx40 expression remains unclear. In this study, we sought to identify polymorphisms in the Cx40 gene GJA5, investigate the potential functional role of these polymorphisms, and determine their allelic frequencies. The prevalence of nonsynonymous Cx40 mutations in blood and atrial tissue was also compared to mutation frequencies reported in prior studies.We conducted direct sequencing of the GJA5 coding and 3' UTR regions in blood samples from 91 lone AF subjects and 67 atrial tissue-derived samples from a lone cohort, a mixed AF cohort, and several transplant donors. Reporter gene transfection and tissue allelic expression imbalance assays were used to assess the effects of a common insertion/deletion polymorphism on Cx40 mRNA stability and expression.We identified one novel synonymous SNP in blood-derived DNA from a lone AF subject. In atrial tissue-derived DNA from lone and mixed AF subjects, we observed one novel nonsynonymous SNP, one rare previously reported synonymous SNP, and one novel 3' UTR SNP. A previously noted 25 bp insertion/deletion polymorphism in the 3' UTR was found to be common (minor allele frequency = 0.45) but had no effect on Cx40 mRNA stability and expression. The observed prevalence of nonsynonymous Cx40 mutations in atrial tissues derived from lone AF subjects differed significantly (p = 0.03) from a prior atrial tissue study reporting a high mutation frequency in a group of highly selected young lone AF subjects.Our results suggest that Cx40 coding SNPs are uncommon in AF populations, although rare mutations in this gene may certainly lead to AF pathogenesis. Furthermore, a common insertion/deletion polymorphism in the Cx40 3' UTR does not appear to play a role in modulating Cx40 mRNA levels.

Dataset Information

CYP11B2 T-344C gene polymorphism and atrial fibrillation: a meta-analysis of 2,758 subjects.

Background

Objective and methods

Results

Conclusions

Publications

CYP11B2 T-344C gene polymorphism and atrial fibrillation: a meta-analysis of 2,758 subjects.

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