Association of genetic variants with atrial fibrillation

Abstract

Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ test revealed that rs599839 (→) of the proline/serine-rich coiled-coil 1 gene (PSRC1, P=0.0084) and rs11556924 (→, Arg363His) of the zinc finger, C3HC-type containing 1 gene (ZC3HC1, P=0.0076) were significantly (P<0.01) associated with atrial fibrillation. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, estimated glomerular filtration rate, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidemia revealed that rs599839 (P=0.0043; odds ratio, 1.56; dominant model) and rs11556924 (P=0.0043; odds ratio, 1.93; dominant model) were significantly associated with atrial fibrillation, with the minor and alleles, respectively, representing risk factors for this condition. PSRC1 and ZC3HC1 may thus be susceptibility loci for atrial fibrillation in Japanese individuals.

The Coronary Artery Disease-associated Coding Variant in Zinc Finger C3HC-type Containing 1 (ZC3HC1) Affects Cell Cycle Regulation

“…Furthermore, rs11556924 is a coding SNP in the ZC3HC1 gene, resulting in an arginine-histidine polymorphism at amino acid residue 363 in the NIPA (Nuclear Interaction Partner of ALK) protein encoded by ZC3HC1 ( 8 ). rs11556924 has also been associated with altered carotid intima-media thickness in patients with rheumatoid arthritis ( 9 ) and with altered risk of atrial fibrillation ( 10 ). The Arg-363 allele is the more common allele (allele frequency = 0.62) ( 7 ) and is associated with a 9% increase in CAD risk per allele.…”