Variation in the sodium-dependent vitamin c transporter 2 gene is associated with risk of acute coronary syndrome among women

Background: The sodium-dependent vitamin C transporter 2 (SVCT2) is responsible for the transport of vitamin C into cells, and malfunction of this protein leads to reduced vitamin C uptake in the arterial wall. We tested the hypothesis that candidate variations rs6139591 and rs1776964 in the SVCT2 coding gene (SLC23A2) are associated with development of acute coronary syndrome. Design: In the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among subjects aged 50-64 years. Results: 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 rs6139591 TT women with an estimated dietary vitamin C intake below the median had a higher risk of acute coronary syndrome compared with female CC homozygotes (adjusted HR 5.39, 95% CI, 2.01-14.50). For rs1776964, we again found a higher risk (adjusted HR 3.45, 95% CI, 1.16–10.28) among TT-homozygous women with above-median vitamin C intakes, as compared with the CC genotype and low vitamin C intake. Among men, weaker and non-significant associations were observed for both polymorphisms. Conclusion: 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 be partially compensated by a higher dietary intake of vitamin C. Sufficient vitamin C intake is therefore particularly important in genetic SVCT subgroups.