Assessment of association of rs2200733 on chromosome 4q25 with atrial fibrillation and ischemic stroke in a Chinese Han population

Abstract

Atrial fibrillation (AF) is the most common arrhythmia in the clinical setting and an independent risk factor for stroke. Approximately 10 million Chinese people are affected by AF, but the genetic basis is largely unknown. A recent genome-wide association study in Iceland identified association between SNP rs2200733 on 4q25 and AF; however, many independent replication studies are essential to unequivocally validate this association. To assess the association between rs2200733 and AF as well as that between rs2200733 and ischemic stroke in a mainland Chinese Han population, we carried out case-control association studies with 383 AF patients versus 851 non-AF controls and 811 ischemic stroke patients versus 688 non-stroke controls. Highly significant association was detected between rs2200733 and AF in a Chinese Han population (allelic P = 3.7 × 10(-11) with OR = 1.81; genotypic P = 4.1 × 10(-12) with a dominant model). When the AF cases were divided into lone AF (32.6%) and other types of AF (67.4%), significantly stronger association was found with lone AF (OR = 2.40, P = 1.3 × 10(-9) compared to OR = 1.59, P = 6.2 × 10(-7) for other types of AF; P = 0.02 for two ORs). No significant association was found between rs2200733 and ischemic stroke. Our results suggest that SNP rs2200733 confers a highly significant risk of AF, but not ischemic stroke, in a more representative Chinese Han population in the mainland China.

The Association of the 4q25 Susceptibility Variant for Atrial Fibrillation With Stroke Is Limited to Stroke of Cardioembolic Etiology

“…3 A small replication study in the Chinese Han population failed to show association for ischemic stroke. 7 The 4q25 variants had been shown previously to confer risk for atrial fibrillation (AF). 8 The 4q25 haplotype block consists of Ϸ1.5 million bp without any known genes.…”

Genetics of Atrial Fibrillation

“…rs2200733 was the most significantly associated polymorphism. The association between rs2200733 and AF has since been replicated in GWAS involving cohorts of Asian patients as well as patients of European ancestry [25,26,60,61]. Neither variant at the 4q25 locus has been correlated with AF risk factors such as obesity, hypertension, or myocardial infarction.…”

Common variants for atrial fibrillation: results from genome-wide association studies

“…In sum, these studies consistently showed the association between rs2200733 and AF but not with rs10033464. Shi et al (Shi et al 2009) also carried out a case-control study with AF patients and non-AF controls to conWrm the association of rs2200733 on chromosome 4q25 with AF in a Chinese Han population. They conWrmed a signiWcant association with OR = 1.81 between rs2200733 and AF (Shi et al 2009).…”