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C-Reactive Protein Gene Polymorphisms and the Risk of Atrial Fibrillation in a Chinese Population in Taiwan.

ABSTRACT: BACKGROUND:Elevated plasma C-reactive protein (CRP) levels can be used to predict an increased risk of future atrial fibrillation (AF). However, several single polynucleotide polymorphisms (SNPs) in the CRP gene affect CRP levels. This study aims to elucidate the correlation between CRP gene polymorphisms and the risk of AF among a Chinese population in Taiwan. METHODS:A total of 200 patients with AF and 240 age- and gender-comparable control subjects were enrolled in this study. From these patients, five SNPs in the CRP gene were selected and genotyped. RESULTS:Patients with AF had significantly higher plasma CRP levels than the controls. In the total study population, the minor alleles of rs3091244 and rs1205 were significantly associated with higher CRP level (p = 0.001 and 0.045, respectively). The frequency of rs1800947 minor allele (C) was significantly higher in patients with AF than that in control subjects (12.8% and 4.6%, respectively; p < 0.001). On multivariate analysis, the presence of the C allele of rs1800947 was significantly and independently associated with AF after adjustment for age, gender, body mass index, hypertension, diabetes, smoking, hypercholesterolemia, coronary artery disease, concomitant medication, and CRP levels (odds ratio = 3.21; 95% confidence interval = 1.54-6.68; p = 0.01). Haplotype analysis further verified that the rs3091244C and rs1800947C bi-loci haplotype was significantly overpresented in patients with AF than in the controls. CONCLUSIONS:Our results suggest that the presence of the C allele of rs1800947 may indicate susceptibility to AF in a Chinese population in Taiwan. KEY WORDS:Atrial fibrillation; C-reactive protein; Polymorphism.

SUBMITTER: Tung YC

PROVIDER: S-EPMC4804832 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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C-Reactive Protein Gene Polymorphisms and the Risk of Atrial Fibrillation in a Chinese Population in Taiwan.

Tung Ying-Chang YC Wu Lung-Sheng LS Chen Wei-Jan WJ Kuo Chi-Tai CT Wang Chun-Li CL Chang Chi-Jen CJ Tsai Hsin-Yi HY Yeh Yung-Hsin YH Hsu Lung-An LA

Acta Cardiologica Sinica 20130501 3

<h4>Background</h4>Elevated plasma C-reactive protein (CRP) levels can be used to predict an increased risk of future atrial fibrillation (AF). However, several single polynucleotide polymorphisms (SNPs) in the CRP gene affect CRP levels. This study aims to elucidate the correlation between CRP gene polymorphisms and the risk of AF among a Chinese population in Taiwan.<h4>Methods</h4>A total of 200 patients with AF and 240 age- and gender-comparable control subjects were enrolled in this study. ...[more]

PMID: 27122709

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Project description:BackgroundPR interval variations have recently been associated with an increased risk of long-term atrial fibrillation (AF), heart block and all-cause mortality. Genome-wide association studies have linked the PR interval with several common variants in the TBX5 gene. Several variants in the TBX5 gene, including rs7312625 and rs883079, have been associated with AF. The purpose of this study was to determine the association of single-nucleotide polymorphisms (SNPs) in the TBX5 gene, rs7312625 and rs883079, with AF in Chinese Han patients.Methodology/principal findingsIn this case-control association study, large cohorts of AF patients (n = 1132) and controls (n = 1206) were recruited from different hospitals. The genotyping was performed using a Rotor-Gene TM 6000 high-resolution melt system. Rs7312625, rs3825214 and rs883079 were analyzed. We found that SNP 3825214 was significantly associated with AF (P-obs = 0.002, odds ratio [OR] = 0.82), and lone AF (P-obs = 6.77x10-5, odds ratio [OR] = 0.71). SNP rs7312625 was significantly associated with lone AF (P-obs = 0.015, odds ratio [OR] = 1.27), although its association with AF was not significant. No significant association of SNP rs883079 with AF or lone AF was observed. Thus, we analyzed the interaction among these three loci. We demonstrated significant interaction among rs3825214, rs7312625 and rs883079. Four-locus risk alleles showed the highest odds ratio in combined rs3825214 and rs7312625 (P-obs<0.0001, odds ratio [OR] = 2.21). Six-locus risk alleles showed the highest odds ratio in combined rs3825214, rs7312625 and rs 883079(P-obs<0.0001, odds ratio [OR] = 2.35). Significance was established with the trend test (P<0.0001).ConclusionsFor the first time, we report the strong association of SNP rs3825214 in the TBX5 gene with AF and lone AF in a Chinese Han population. Rs7312625 was significantly associated with lone AF, and snp-snp interaction increased the risk of atrial fibrillation. Our data might provide new insights into understanding AF pathogenesis and designing novel genetic therapies for AF patients.

Project description:AimsAtrial fibrillation (AF) is a frequent co-morbidity in heart failure (HF) associated with increased mortality, but little is known about the mechanisms underlying AF onset in HF patients. We evaluated the association of cardiovascular and genetic risk factors with AF in HF patients.Methods and resultsIndividuals hospitalized for HF (n = 1040; 500 with AF) were identified from a large, population-based cohort study (n = 30 447; 2339 with AF). Genetic polymorphisms in the chromosomal regions 4q25 (rs2200733) and 16q22 (rs2106261) associated with AF in genome-wide association studies were genotyped. Association of cardiovascular risk factors and polymorphisms with AF was tested in HF patients and the entire cohort using both prospective and non-time-dependent models. Cardiovascular risk factors-hypertension, body mass index, sex, smoking, diabetes, and myocardial infarction-were associated with AF in the entire cohort but not in HF patients. In contrast, polymorphisms on chromosomes 16q22 and 4q25 were associated with AF both in the entire cohort and in HF patients, conferring 75% [95% confidence interval (CI) 35-126, P = 2 × 10(-5)] and 57% (95% CI 18-109, P = 0.002) increased risk of AF per copy in HF patients, respectively. In the entire cohort, AF risk in the presence of HF was multiplicatively magnified by genotype for 16q22 (P for interaction = 7 × 10(-4)) but not 4q25 (P = 0.83). In prospective analyses excluding patients with AF diagnosis prior to or simultaneously with HF diagnosis, 16q22 but not 4q25 remained robustly associated with AF (hazard ratio 1.96, 95% CI 1.40-2.73, P = 8 × 10(-5)). The proportion of AF diagnoses in HF patients attributable to polymorphisms was 19% and 12%, respectively.ConclusionsA polymorphism in the ZFHX3 gene, encoding a cardiac transcription factor, was associated with increased AF risk in HF patients, and the genetic association with AF was more pronounced in HF patients than in the general population.

Dataset Information

C-Reactive Protein Gene Polymorphisms and the Risk of Atrial Fibrillation in a Chinese Population in Taiwan.

Publications

C-Reactive Protein Gene Polymorphisms and the Risk of Atrial Fibrillation in a Chinese Population in Taiwan.

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