The single nucleotide polymorphisms of Kir3.4 gene and their correlation with lone paroxysmal atrial fibrillation in Chinese Han population.
BACKGROUND
Acetylcholine induced inwardly rectifying current (I(KACh)) is a heteromultimeric complex formed by Kir3.1 and Kir3.4 subunits and plays important roles in the development of atrial fibrillation (AF). AF is a common disorder among Chinese, the frequency of AF is about 0.61%, and in patients with strokes it is 12.1%. We hypothesise that lone paroxysmal AF genetic variation in Kir3.4 may predispose the atria to fibrillation in the Chinese population.


METHODS
We recruited 186 patients with lone paroxysmal AF, and 210 matched controls by age (49.61+/-8.04 years), sex, smoking habit, and left atrial dimension in Zhejiang Province, China. Genotype of Kir3.4 was determined with polymerase chain reaction (PCR) and direct sequencing. The SPSS statistical software was used for chi(2) test. LD and haplotypes were calculated using SHESIS software package.


RESULTS
Three synonymous known single nucleotide polymorphisms (SNPs) in Kir3.4 were genotyped, including C171T (rs6590357), G810T (rs7118824) and C834T (rs7118833). We found low levels of linkage disequilibrium (LD) between C171T and G810T (D'=0.272), complete LD between SNPs G810T and C834T (D'=1) in AF patients and controls. The case-control analysis revealed that the frequency of genotype and allele in three SNPs are significantly different between lone paroxysmal AF patients than in control subjects. The odds ratio (OR) for AF 171T and 810T alleles were 1.546 (95% CI 1.015-2.355) and 1.520 (95% CI 1.012-2.284), respectively, when compared with patients without Kir3.4T alleles in these two loci. The OR for AF in patients with C-T genotype were 13.364 (95% CI 5.710-31.278) and 37.135 (95% CI 9.050-152.381) when comparing patients with T-G genotype.


CONCLUSIONS
Our findings suggest that C171T and G810T SNPs in Kir3.4 gene might be risk factors for lone paroxysmal AF in Chinese population.
Zhang
Chuan
C
Department of Cardiovascular Internal Medicine, Huzhou Central Hospital, Huzhou, Zhejiang Province, China. Zhangchuan1973@yahoo.cn
Yuan
Gao-Hui
GH
Cheng
Zhen-Feng
ZF
Xu
Min-Wen
MW
Hou
Li-Fang
LF
Wei
Fan-Ping
FP
D000328:Adult; D001281:Atrial Fibrillation / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; C484274:KCNJ5 protein, human