Polymorphisms of renin-angiotensin-aldosterone system gene in chinese han patients with nonfamilial atrial fibrillation.
BACKGROUND
Atrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.


METHODS
A total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.


RESULTS
In single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared 'TT' haplotype with the common 'TC' haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with 'TC', carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with 'TT' haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.


CONCLUSIONS
Via a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor.
Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China.
Li-Qun
LQ
Zhao
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China.
Zu-Jia
ZJ
Wen
Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China.
Yong
Y
Wei
Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China.
Juan
J
Xu
Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China.
Zheng
Z
Chen
Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China.
Bao-Zhen
BZ
Qi
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai 201203, China.
Zhimin
Z
Wang
Department of Genetics, Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center and Shanghai Industrial Technology Institute (SITI), Shanghai 201203, China.
Zhi-Ming
ZM
Wang
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, 200030, China.
Yong-Yong
YY
Shi
Department of Cardiology, Shanghai First People's Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China.
Shao-Wen
SW
Liu
D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics*; D001281:Atrial Fibrillation / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012084:Renin-Angiotensin System / Q000235:genetics*