Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
PLoS One. 2013 Aug 21;8(8):e70421. doi: 10.1371/journal.pone.0070421. eCollection 2013.
Vitamin C is associated with a lower risk of coronary heart disease possibly due to its anti-oxidative effects, beneficial effects on endothelial function and importance in collagen synthesis. The sodium-dependent vitamin C transporter 2 is responsible for the transport of vitamin C into various cells and malfunction of this protein leads to reduced vitamin C in tissue, including the arterial wall. We tested the hypothesis that candidate variations rs6139591 and rs1776964 in the gene coding for sodium-dependent vitamin C transporter 2 are associated with development of acute coronary syndrome.
In the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among 57,053 subjects aged 50-64 years.
During a mean follow-up period of 6.4 years, we identified 936 cases and randomly selected a sub-cohort (n = 1,580) with full information on genotypes and covariates. Using Cox proportional hazard models, we found that women with the rs6139591 TT genotype and a lower than median dietary vitamin C intake had a higher risk of acute coronary syndrome compared with those with the CC genotype (adjusted HR 5.39, 95% confidence interval, 2.01-14.50). We also observed a not as strong but positive although inconsistent association for women at a higher than median intake of vitamin C rich food. For the rs1776964 polymorphism, we found a higher risk (adjusted HR 3.45, 95% CI, 1.16-10.28) among TT-homozygous women with higher than median vitamin C intake compared with the CC genotype and low vitamin C intake. Among men, weaker and non-significant associations were observed for both polymorphisms.
Genetic variation in the sodium-dependent vitamin C transporter 2 is associated with risk of incident acute coronary syndrome in women. The genotype effects may not be fully compensated by a higher intake of vitamin C rich food.
维生素 C 与冠心病风险降低相关，这可能是由于其抗氧化作用、对血管内皮功能的有益影响以及在胶原蛋白合成中的重要性。钠离子依赖的维生素 C 转运蛋白 2 负责将维生素 C 转运到各种细胞中，该蛋白的功能障碍会导致组织中维生素 C 减少，包括动脉壁。我们检验了这样一个假设，即钠离子依赖的维生素 C 转运蛋白 2 基因中的候选变异 rs6139591 和 rs1776964 与急性冠状动脉综合征的发生有关。
在丹麦饮食、癌症与健康队列研究中，我们对 57053 名年龄在 50-64 岁的受试者进行了病例-对照研究。
在平均 6.4 年的随访期间，我们确定了 936 例病例，并随机选择了一个亚队列（n=1580），其中包含基因型和协变量的完整信息。使用 Cox 比例风险模型，我们发现 rs6139591 TT 基因型且维生素 C 摄入量低于中位数的女性发生急性冠状动脉综合征的风险高于 CC 基因型（调整后的 HR 5.39，95%可信区间 2.01-14.50）。我们还观察到，对于维生素 C 丰富食物摄入量高于中位数的女性，这种关联虽然不那么强烈但呈阳性，而且不一致。对于 rs1776964 多态性，我们发现与 CC 基因型和低维生素 C 摄入量相比，维生素 C 摄入量高于中位数的 TT 纯合子女性发生的风险更高（调整后的 HR 3.45，95%CI，1.16-10.28）。在男性中，两种多态性的相关性较弱且无统计学意义。
钠离子依赖的维生素 C 转运蛋白 2 的遗传变异与女性发生急性冠状动脉综合征的风险相关。基因型的影响可能不能完全由维生素 C 丰富食物的高摄入量来补偿。
