Jabbari Javad, Olesen Morten S, Holst Anders G, Nielsen Jonas B, Haunso Stig, Svendsen Jesper H
Danish National Research Foundation Centre for Cardiac Arrhythmia (DARC), Heart Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Cardiology. 2011;118(2):116-20. doi: 10.1159/000323840. Epub 2011 May 9.
The aim of this study was to screen lone atrial fibrillation (AF) patients for mutations in the genes KCNJ2, KCNJ3 and KCNJ5, all encoding potassium channels. Furthermore, we wanted to replicate the prior association of two single-nucleotide polymorphisms (SNPs) in KCNJ5, C171T (rs6590357) and G810T (rs7118824), with lone AF in Han Chinese.
We sequenced the coding region and splice site of KCNJ2, KCNJ3 and KCNJ5 in 187 early-onset lone-AF patients screening for mutations and counting SNP frequencies for the two noted SNPs in KCNJ5.
No mutations were found in KCNJ2, KCNJ3 or KCNJ5. Both genotype distribution and allele frequencies of the SNPs rs6590357 and rs7118824 significantly differed between the AF and control group (p(genotype) = 0.0067, p(allele) = 0.0021 and p(genotype) = 0.014, p(allele) = 0.0101, respectively). On allele level, the OR for lone AF for rs6590357 was 1.77 (95% CI 1.16-2.73, p = 0.009) and for rs7118824 it was 1.71 (95% CI 1.13-2.57, p = 0.01) in a model adjusted for age and gender.
Our findings indicate that rs6590357 and rs7118824 in KCNJ5 are associated with early-onset lone AF in Caucasians. No mutations were found in the exon or splice site of KCNJ2, KCNJ3 or KCNJ5.
本研究旨在筛查孤立性心房颤动(AF)患者中KCNJ2、KCNJ3和KCNJ5基因的突变,这三个基因均编码钾通道。此外,我们想要在汉族人群中复现KCNJ5基因中两个单核苷酸多态性(SNP),即C171T(rs6590357)和G810T(rs7118824)与孤立性AF的先前关联。
我们对187例早发性孤立性AF患者的KCNJ2、KCNJ3和KCNJ5基因的编码区和剪接位点进行测序,以筛查突变,并计算KCNJ5基因中上述两个SNP的SNP频率。
在KCNJ2、KCNJ3或KCNJ5基因中未发现突变。AF组和对照组中SNP rs6590357和rs7118824的基因型分布和等位基因频率均有显著差异(p(基因型)=0.0067,p(等位基因)=0.0021;以及p(基因型)=0.014,p(等位基因)=0.0101)。在年龄和性别校正模型中,rs6590357的孤立性AF等位基因水平OR值为1.77(95%CI 1.16 - 2.73,p = 0.009),rs7118824的OR值为1.71(95%CI 1.13 - 2.57,p = 0.01)。
我们的研究结果表明,KCNJ5基因中的rs6590357和rs7118824与白种人的早发性孤立性AF相关。在KCNJ2、KCNJ3或KCNJ5基因的外显子或剪接位点未发现突变。