Genetic Loci on Chromosomes 4q25, 7p31, and 12p12 Are Associated With Onset of Lone Atrial Fibrillation Before the Age of 40 Years
Genetic Loci on Chromosomes 4q25, 7p31, and 12p12 Are Associated With Onset of Lone Atrial Fibrillation Before the Age of 40 Years
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DOI：
10.1016/j.cjca.2011.11.016
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发表时间：
2012-03-01
影响因子：
6.2
通讯作者：
Svendsen, Jesper H.
中科院分区：
文献类型：
--
作者：
Olesen, Morten S.;Holst, Anders G.;Svendsen, Jesper H.
背景资料：在全基因组关联研究（GWAS）中，染色体1 q21、4 q25和16 q22上的三个不同遗传位点与房颤（AF）相关。另外五个位点主要与PR间期相关，随后与AF相关。我们的目的是研究8个单核苷酸多态性（SNP）是否与早发性孤立性AF相关，这些SNP代表了先前在全基因组关联研究中与AF相关的8个基因组位点。我们纳入了209例早发性孤立性房颤患者和534例无房颤患者作为对照组。采用TaqMan分析法对8个SNP进行基因分型结果：发现三个SNP与早发性孤立性AF显著相关：rs 2200733最接近PITX 2（比值比[OR]，1.62; 95%置信区间[CI]，1.16-2.27; P = 0.004），rs3807989接近CAV 1 rs 11047543接近SOX 5（OR 1.70; 95%CI 1.18-2.44; P = 0.004）。当校正多重检验时，rs 2200733和rs 11047543仍然与房颤显著相关。三个SNP，rs 2200733（4 q25）、rs3807989（7 p31）和rs 11047543（12 p12），与早发性孤立性AF相关。所有3个SNP都位于靠近先前研究中已证明对心脏形态/发育重要的基因，从而表明这些SNPs与结构性心脏病之间的联系。然而，我们的研究结果表明，这3个基因座的变异与AF相关的机制不涉及心脏的主要结构异常。
Background: Three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 have been associated with atrial fibrillation (AF) in genome-wide association studies (GWAS). Five additional loci have been associated primarily with the PR interval and subsequently with AF. We aimed to investigate if 8 single nucleotide polymorphisms (SNPs), representing the 8 genomic loci previously linked with AF in genome-wide association studies, were associated with early-onset lone AF.Methods: We included 209 patients with early-onset lone AF, and a control group consisting of 534 individuals free of AF. The 8 SNPs were genotyped using TaqMan assays (Applied Biosystems, Foster City, CA).Results: Three SNPs were found to be significantly associated with early-onset lone AF: rs2200733 closest to PITX2 (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.16-2.27; P = 0.004), rs3807989 near to CAV1 (OR 1.35; 95% CI, 1.06-1.72; P = 0.015), and rs11047543 near to SOX5 (OR 1.70; 95% CI, 1.18-2.44; P = 0.004). When correcting for multiple testing, rs2200733 and rs11047543 were still significantly associated with AF.Conclusions: Three SNPs, rs2200733 (4q25), rs3807989 (7p31), and rs11047543 (12p12), were associated with early-onset lone AF. All 3 SNPs are positioned close to genes that in previous studies have been demonstrated to be important for cardiac morphology/development, thereby suggesting a link between these SNPs and structural heart disease. Our results however, indicate that variants in these 3 loci are associated with AF through mechanisms that do not involve major structural abnormalities in the heart.