Genetically deprived vitamin D exposure predisposes to atrial fibrillation

Aims Low vitamin D level is associated with atrial fibrillation (AF) and may be implicated in its pathogenesis. Methods and results We studied single nucleotide polymorphisms (SNPs) of vitamin D mechanistic pathways and serum 25-hydroxyvitamin D [25(OH) D] levels in an age- and gender-matched case-control study (controls without AF: mean age 68.6 +/- 8.7 years, female 25%; n = 1019; with AF: mean age 69.7 +/- 9.5 years, female 30%; n = 156) recruited from a Chinese clinical cohort of patients with stable coronary artery disease. Twelve SNPs involved in the vitamin D mechanistic pathways were studied [biosynthetic: rs4646536, rs10877012, rs3829251, rs1790349; activation: rs2060793, rs1993116; vitamin D-binding protein (VBP)/group-specific component (GC): rs4588, rs7041, rs2282679, rs1155563; and vitamin D receptor: rs1544410, rs10735810]. A genetic risk score (GRS) (0-8) was constructed from SNPs associated with serum 25(OH) D as a proxy to lifelong vitamin D-deficient state. All 4 SNPs involved in the VBP/GC were significantly associated with serum 25(OH) D (rs4588, P<0.001; rs2282679, P<0.001; rs7041, P = 0.011; rs1155563, P<0.001; all other SNPs, P > 0.05). Vitamin D GRS (points 0-8) generated from these 4 SNPs was independently predictive of serum 25(OH) D [B = 0.54, 95% confidence interval (CI) 0.30-0.79; P<0.001]. Genetically deprived vitamin D status as denoted by a low GRS (0-3) independently predicted an increased risk of AF, compared to a high GRS (4-8) (odds ratio = 1.848, 95% CI 1.217-2.805; P = 0.004). Conclusion Genetically deprived vitamin D exposure predisposes to increased AF among patients with coronary artery disease. Whether VBP/GC may alter the risk of AF via alternative mechanisms warrants further studies.