Zhang Chuan, Yuan Gao-Hui, Cheng Zhen-Feng, Xu Min-Wen, Hou Li-Fang, Wei Fan-Ping
Department of Cardiovascular Internal Medicine, Huzhou Central Hospital, Huzhou, Zhejiang Province, China.
Heart Lung Circ. 2009 Aug;18(4):257-61. doi: 10.1016/j.hlc.2008.12.002. Epub 2009 Feb 8.
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.
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.
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.
Our findings suggest that C171T and G810T SNPs in Kir3.4 gene might be risk factors for lone paroxysmal AF in Chinese population.
乙酰胆碱诱导的内向整流电流（I(KACh)）是一种由Kir3.1和Kir3.4亚基形成的异源多聚体复合物，在心房颤动（AF）的发生发展中起重要作用。AF在中国人群中是一种常见疾病，AF的发生率约为0.61%，在中风患者中为12.1%。我们推测，Kir3.4基因的孤立阵发性AF遗传变异可能使中国人群的心房易发生颤动。
我们在中国浙江省招募了186例孤立阵发性AF患者和210例年龄（49.61±8.04岁）、性别、吸烟习惯和左心房大小相匹配的对照。采用聚合酶链反应（PCR）和直接测序法测定Kir3.4的基因型。使用SPSS统计软件进行卡方检验。使用SHESIS软件包计算连锁不平衡（LD）和单倍型。
对Kir3.4基因中的三个同义已知单核苷酸多态性（SNP）进行了基因分型，包括C171T（rs6590357）、G810T（rs7118824）和C834T（rs7118833）。我们发现AF患者和对照中C171T与G810T之间的连锁不平衡（LD）水平较低（D'=0.272），SNP G810T与C834T之间完全连锁不平衡（D'=1）。病例对照分析显示，孤立阵发性AF患者中三个SNP的基因型和等位基因频率与对照受试者相比有显著差异。与这两个位点无Kir3.4T等位基因的患者相比，AF的171T和810T等位基因的比值比（OR）分别为1.546（95%CI 1.015-2.355）和1.520（95%CI 1.012-2.284）。与T-G基因型患者相比，C-T基因型患者AF的OR分别为13.364（95%CI 5.710-31.278）和37.135（95%CI 9.050-152.381）。
我们的研究结果表明，Kir3.4基因中的C171T和G810T SNP可能是中国人群孤立阵发性AF的危险因素。
