Genetically deprived vitamin D exposure predisposes to atrial fibrillation.
Europace. 2017 Dec 1;19(suppl_4):iv25-iv31. doi: 10.1093/europace/eux312.
Chan YH1, Yiu KH1,2, Hai JJ1, Chan PH1, Lam TH3, Cowling BJ3, Sham PC4, Lau CP1, Lam KS2,5, Siu CW1,2, Tse HF1,2.
1 Division of Cardiology, Queen Mary Hospital, The U. of Hong Kong, Hong Kong SAR, China.
2 Research Center of Heart, Brain, Hormone and Healthy Ageing, The U. of Hong Kong, Hong Kong SAR, China.
3 School of Public Health, The U. of Hong Kong, Hong Kong SAR, China.
4 Department of Psychiatry and Centre for Genomic Sciences, The U. of Hong Kong, Hong Kong SAR, China.
5 Division of Endocrinology, Queen Mary Hospital, The U. of Hong Kong, Hong Kong SAR, China.
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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.
KEYWORDS:
25-Hydroxyvitamin D; Atrial fibrillation; Genetic polymorphism; Vitamin D-binding protein
PMID: 29220424 DOI: 10.1093/europace/eux312