Division of Cardiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China.
Research Center of Heart, Brain, Hormone and Healthy Ageing, The University of Hong Kong, Hong Kong SAR, China.
Europace. 2017 Dec 1;19(suppl_4):iv25-iv31. doi: 10.1093/europace/eux312.
Low vitamin D level is associated with atrial fibrillation (AF) and may be implicated in its pathogenesis.
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).
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.
维生素 D 水平较低与心房颤动（AF）有关，并且可能参与其发病机制。
我们在一项年龄和性别匹配的病例对照研究（对照组无 AF：平均年龄 68.6±8.7 岁，女性 25%；n=1019；有 AF：平均年龄 69.7±9.5 岁，女性 30%；n=156）中研究了维生素 D 机制途径的单核苷酸多态性（SNP）和血清 25-羟维生素 D [25（OH）D]水平，该研究是从中国稳定型冠状动脉疾病患者的临床队列中招募的。研究了 12 个参与维生素 D 机制途径的 SNP[生物合成：rs4646536、rs10877012、rs3829251、rs1790349；激活：rs2060793、rs1993116；维生素 D 结合蛋白（VBP）/群体特异性成分（GC）：rs4588、rs7041、rs2282679、rs1155563；和维生素 D 受体：rs1544410、rs10735810]。根据与血清 25（OH）D 相关的 SNP 构建了遗传风险评分（GRS）（0-8），作为终生维生素 D 缺乏状态的替代物。所有参与 VBP/GC 的 4 个 SNP 与血清 25（OH）D 显著相关（rs4588，P<0.001；rs2282679，P<0.001；rs7041，P=0.011；rs1155563，P<0.001；所有其他 SNP，P>0.05）。从这 4 个 SNP 生成的维生素 D GRS（点 0-8）可独立预测血清 25（OH）D[B=0.54，95%置信区间（CI）0.30-0.79；P<0.001]。低 GRS（0-3）表示遗传剥夺的维生素 D 状态独立预测冠状动脉疾病患者的 AF 风险增加，而高 GRS（4-8）则相反（比值比=1.848，95%CI 1.217-2.805；P=0.004）。
遗传剥夺的维生素 D 暴露使冠状动脉疾病患者的 AF 风险增加。VBP/GC 是否可以通过其他机制改变 AF 的风险值得进一步研究。
