Abstract 3396: Genetic Risk for Lone Atrial Fibrillation
AIMS Although atrial fibrillation may be caused by electric conduction disturbance and increased hemodynamic stress, the genetic components of this condition remain largely unknown. The purpose of the study was to identify gene polymorphisms that confer susceptibility to atrial fibrillation.
METHODS The study population comprised 1069 unrelated Japanese individuals: 196 subjects with chronic lone atrial fibrillation (153 men, 43 women) and 873 controls (302 men, 571 women). The genotypes for 202 polymorphisms of 153 candidate genes were determined by a method based on the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology.
RESULTS Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia revealed that the C-1306T polymorphism of the matrix metalloproteinase 2 gene (MMP2; odds ratio 1.9), the G/T polymorphism in intron 2 (SNP-276 ) of the adaptor-related protein complex 2, MU-1 subunit gene (AP2M1; odds ratio 2.3), the C-28G polymorphism of the chemokine, CC motif, ligand 5 gene (CCL5; odds ratio 4.9), and the C-511T polymorphism of interleukin 1-beta gene (IL1B; odds ratio 2.1) were significantly (P < 0.005) associated with atrial fibrillation, with variant alleles representing risk factors for this condition. Furthermore, the A-592C polymorphism of the interleukin 10 gene (IL10; odd ratio 0.3) and the G/A (Ala147Thr) polymorphism of the carboxypeptidase B2, plasma gene (CPB2; odds ratio 0.6) were significantly (P < 0.005) associated with atrial fibrillation, with variant alleles being protective against this condition. A stepwise forward selection procedure revealed that MMP2, AP2M1, CCL5, IL10, and CPB2 genotype significantly and independently affected the prevalence of atrial fibrillation.
CONCLUSIONS Genetic variants of MMP2, AP2M1, and CCL5 may be risk factors for atrial fibrillation, whereas variants of IL10 and CPB2 may be protective against this condition. Determination of genotypes for these genes may prove informative for assessment of genetic risk for atrial fibrillation and may contribute to the personalized prevention of this condition.