Association of the MYH6 Gene Polymorphism with the Risk of Atrial Fibrillation and Warfarin Anticoagulation Therapy

Abstract

Objective: To study the associations of single nucleotide polymorphisms (SNP) of the myosin heavy chain 6 (MYH6) gene with the risk of atrial fibrillation (AF) and warfarin anticoagulation therapy. Methods: Sanger sequencing was employed to analyze the genotypes of the MYH6 gene's rs28730771, rs365990, and rs2277473 loci in 243 AF patients and 243 non-AF patients (control group) selected according to the age and sex of AF patients at a 1:1 ratio. A multiple logistic regression analysis was used to analyze the risk factors in AF. SHEsis was adopted to analyze the association between rs28730771, rs365990, rs2277473 haplotypes and susceptibility to AF. The average weekly doses of warfarin administered to AF patients with different genotypes were compared. Results: The T allele at rs28730771 of the MYH6 gene (odds ratio [OR] = 2.82, 95% confidence interval [CI]: 1.73-4.59, p < 0.01), the G allele at rs365990 (OR = 1.65, 95% CI: 1.22-2.24, p < 0.01) and the T allele at rs2277473 (OR = 1.91, 95% CI: 1.25-2.91, p < 0.01) were significantly associated with an elevated risk of AF. The results of a logistic regression analysis demonstrated that hypertension, smoking, drinking, family history of stroke, as well as the genotypes at the rs28730771, rs365990, and rs2277473 loci were all risk factors in AF (p < 0.05). The CAG haplotype for the three SNPs was associated with a reduced risk of AF susceptibility (OR = 0.61, 95% CI: 0.46-0.81, p < 0.01), and the CGG haplotype was related to an increased risk of AF (OR = 1.49, 95% CI: 1.07-2.06, p = 0.02). The doses of warfarin used in AF patients with different genotypes at the MYH6 rs28730771, rs365990, and rs2277473 loci were significantly different (p < 0.05). Conclusion: The three SNPs (rs28730771, rs365990, and rs2277473) of the MYH6 gene loci were significantly associated with the risk of AF susceptibility and the dose of warfarin anticoagulant therapy.