Kääb Stefan, Darbar Dawood, van Noord Charlotte, Dupuis Josée, Pfeufer Arne, Newton-Cheh Christopher, Schnabel Renate, Makino Seiko, Sinner Moritz F, Kannankeril Prince J, Beckmann Britt M, Choudry Subbarao, Donahue Brian S, Heeringa Jan, Perz Siegfried, Lunetta Kathryn L, Larson Martin G, Levy Daniel, MacRae Calum A, Ruskin Jeremy N, Wacker Annette, Schömig Albert, Wichmann H-Erich, Steinbeck Gerhard, Meitinger Thomas, Uitterlinden André G, Witteman Jacqueline C M, Roden Dan M, Benjamin Emelia J, Ellinor Patrick T
Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Eur Heart J. 2009 Apr;30(7):813-9. doi: 10.1093/eurheartj/ehn578. Epub 2009 Jan 13.
A recent genome-wide association study identified a haplotype block on chromosome 4q25 associated with atrial fibrillation (AF). We sought to replicate this association in four independent cohorts.
The Framingham Heart Study and Rotterdam Study are community-based longitudinal studies. The Vanderbilt AF Registry and German AF Network (AFNet) are case-control studies. Participants with AF (n = 3508) were more likely to be male and were older than referent participants (n = 12 173; Framingham 82 +/- 10 vs. 71 +/- 13 years; Rotterdam 73 +/- 8 vs. 69 +/- 9 years; Vanderbilt 54 +/- 14 vs. 57 +/- 14 years; AFNet 62 +/- 12 vs. 49 +/- 14 years). Single nucleotide polymorphism (SNP) rs2200733 was associated with AF in all four cohorts, with odds ratios (ORs) ranging from 1.37 in Rotterdam [95% confidence interval (CI) 1.18-1.59; P = 3.1 x 10(-5)] to 2.52 in AFNet (95% CI 2.22-2.8; P = 1.8 x 10(-49)). There also was a significant association between AF and rs10033464 in Framingham (OR 1.34; 95% CI 1.03-1.75; P = 0.031) and AFNet (OR 1.30; 95% CI 1.13-1.51; P = 0.0002), but not Vanderbilt (OR 1.16; 95% CI 0.86-1.56; P = 0.33). A meta-analysis of the current and prior AF studies revealed an OR of 1.90 (95% CI 1.60-2.26; P = 3.3 x 10(-13)) for rs2200733 and of 1.36 (95% CI 1.26-1.47; P = 6.7 x 10(-15)) for rs10033464.
The non-coding SNPs rs2200733 and rs10033464 are strongly associated with AF in four cohorts of European descent. These results confirm the significant relations between AF and intergenic variants on chromosome 4.
最近一项全基因组关联研究确定了4号染色体q25上一个与心房颤动（AF）相关的单倍型块。我们试图在四个独立队列中重复这一关联。
弗雷明汉心脏研究和鹿特丹研究是基于社区的纵向研究。范德比尔特房颤登记处和德国房颤网络（AFNet）是病例对照研究。房颤患者（n = 3508）更可能为男性，且比对照参与者年龄大（n = 12173；弗雷明汉82±10岁对71±13岁；鹿特丹73±8岁对69±9岁；范德比尔特54±14岁对57±14岁；AFNet 62±12岁对49±14岁）。单核苷酸多态性（SNP）rs2200733在所有四个队列中均与房颤相关，优势比（OR）范围从鹿特丹的1.37[95%置信区间（CI）1.18 - 1.59；P = 3.1×10⁻⁵]到AFNet的2.52（95% CI 2.22 - 2.8；P = 1.8×10⁻⁴⁹）。在弗雷明汉（OR 1.34；95% CI 1.03 - 1.75；P = 0.031）和AFNet（OR 1.30；95% CI 1.13 - 1.51；P = 0.0002）中，房颤与rs10033464也存在显著关联，但在范德比尔特队列中无关联（OR 1.16；95% CI 0.86 - 1.56；P = 0.33）。对当前及先前房颤研究的荟萃分析显示，rs2200733的OR为1.90（95% CI 1.60 - 2.26；P = 3.3×10⁻¹³），rs10033464的OR为1.36（95% CI 1.26 - 1.47；P = 6.7×10⁻¹⁵）。
非编码SNP rs2200733和rs10033464在四个欧洲裔队列中与房颤密切相关。这些结果证实了房颤与4号染色体上基因间变异之间的显著关系。
