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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.

Warfarin is the most commonly used oral anti-coagulant in clinic practice. However, it is difficult to recommend the correct dosage due to its narrow therapeutic window. The aim of the present study was to verify the clinical value of the Lou type equation, using pharmacogenetics‑based warfarin dosing algorithms to appropriately predict the actual maintenance dose. A total of 87 Chinese Han patients who required treatment with warfarin were enrolled and randomly divided into the experimental and control groups. In the experimental group, the first 3 doses of warfarin were calculated according to the Lou type equation. While in the control group, these 3 treatments were performed following the doctors' recommendations. Then the dose of warfarin was gradually adjusted to the stable dose according to the changes in the international standardized ratio. At the end of the 50 day experimental period, there were a greater number of patients in the experimental group who exhibited a stable blood concentration of warfarin than those in the control group (83.35 and 64.4%, respectively). In addition, the mean and median times for patients to obtain a stable dose in the experimental group were significantly shorter than those in the control group (mean, 18.2±1.7 and 27.3±2.0 days; and median, 11.7±1.1 and 20.5±1.8 days, respectively). The adverse reaction rate of the experimental group (9.5%) was markedly lower than that of the control group (26.7%). The occurrence of adverse reactions in the experimental group was also significantly later when compared with the control group (43.9±1.6 and 38.6±1.5 days, respectively). Furthermore, there was no significant difference between the average predicted dose (3.4±1.1 mg/day) and the average actual dose (3.5±1.4 mg/day; P=0.313). In conclusion, using the Lou type warfarin pharmacokinetic dosing algorithm equation to administer warfarin markedly shortened the adjustment time of warfarin to reach a stable dose and reduced the adverse reactions rate, thus supporting clinical feasibility.