Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
PLoS One. 2013 Jul 25;8(7):e69080. doi: 10.1371/journal.pone.0069080. Print 2013.
Circulating 25-hydroxyvitamin D (25(OH)D) has been associated with cardiovascular disease (CVD) risk in observational studies. Also, SNPs to explain variation in 25(OH)D have been identified by genome-wide association studies. Detection of direct associations between SNPs that significantly affect 25(OH)D and CVD risk would indicate a causal role of vitamin D, as reverse causation could be excluded and confounding could be better controlled. Thus, a combined analysis of candidate SNPs in relation to circulating 25(OH)D and CVD risk was carried out. A case-cohort study within the EPIC-Germany study was conducted comprising a randomly drawn subcohort of 2,132 subjects (57.9% women, mean age: 50.6 years) and incident cases of myocardial infarction (n=559) and stroke (n=471) that occurred during a mean follow-up duration of 7.6 years. 25(OH)D concentrations were measured by LC-MS/MS in baseline plasma samples. Additionally, eight candidate SNPs were assayed. Associations between 25(OH)D, SNPs and the risks of myocardial infarction and stroke were assessed by multivariable regression analyses. Mean 25(OH)D level was 47.2 nmol/L in the subcohort. Four SNPs were associated with 25(OH)D (p<0.05). In subjects with 25(OH)D levels <25 nmol/L, the risks of CVD as composite endpoint (Hazard Ratio: 1.53, 95% confidence interval: 1.12-2.09), myocardial infarction, and stroke were significantly increased compared to subjects with levels ≥ 50 nmol/L, while no significant linear associations were observed. A SNP score was not related to the risks of total CVD (Hazard Ratio: 1.0, 95% confidence interval: 0.71-1.42), myocardial infarction, or stroke. The same was true concerning single SNPs. Given the lack of association between SNPs and the risks of stroke and myocardial infarction, the present findings do not point to a major causal role of vitamin D in the development of these diseases. However, a detection of modest associations between genetic markers and CVD risk in larger consortia cannot be ruled out.
循环 25-羟维生素 D（25(OH)D）已在观察性研究中与心血管疾病（CVD）风险相关联。此外，通过全基因组关联研究已经确定了解释 25(OH)D 变异的 SNP。如果 SNP 与循环 25(OH)D 和 CVD 风险之间存在直接关联，这将表明维生素 D 的因果作用，因为可以排除反向因果关系并且可以更好地控制混杂因素。因此，进行了与循环 25(OH)D 和 CVD 风险相关的候选 SNP 的联合分析。该研究在 EPIC-Germany 研究中进行了病例对照研究，其中包括一个随机抽取的 2132 名受试者的亚队列（57.9%为女性，平均年龄：50.6 岁）和发生心肌梗死（n=559）和中风（n=471）的病例，平均随访时间为 7.6 年。在基线血浆样本中通过 LC-MS/MS 测量 25(OH)D 浓度。此外，还测定了八个候选 SNP。通过多变量回归分析评估 25(OH)D、SNP 与心肌梗死和中风风险之间的关系。在亚队列中，平均 25(OH)D 水平为 47.2nmol/L。四个 SNP 与 25(OH)D 相关（p<0.05）。在 25(OH)D 水平<25nmol/L 的受试者中，与 25(OH)D 水平≥50nmol/L 的受试者相比，CVD 复合终点（危险比：1.53，95%置信区间：1.12-2.09）、心肌梗死和中风的风险显著增加，而没有观察到显著的线性关联。SNP 评分与总 CVD（危险比：1.0，95%置信区间：0.71-1.42）、心肌梗死或中风的风险无关。单 SNP 也是如此。鉴于 SNP 与中风和心肌梗死风险之间缺乏关联，目前的研究结果并未表明维生素 D 在这些疾病发展中的主要因果作用。然而，在更大的联盟中，不能排除遗传标记与 CVD 风险之间存在适度关联的可能性。
