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Variation in the Sodium-Dependent Vitamin C Transporter 2 Gene Is Associated with Risk of Acute Coronary Syndrome among Women

Dalgård, Christine ; Christiansen, Lene ; Vogel, Ulla ; Dethlefsen, Claus ; Tjønneland, Anne ; Overvad, Kim ;Lionetti, Vincenzo (editor)

PLoS ONE, 2013, Vol.8(8) [Peer Reviewed Journal]

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  • Title:
    Variation in the Sodium-Dependent Vitamin C Transporter 2 Gene Is Associated with Risk of Acute Coronary Syndrome among Women
  • Author/Creator: Dalgård, Christine ; Christiansen, Lene ; Vogel, Ulla ; Dethlefsen, Claus ; Tjønneland, Anne ; Overvad, Kim
  • Lionetti, Vincenzo (editor)
  • Subjects: Research Article ; Biology ; Medicine
  • Is Part Of: PLoS ONE, 2013, Vol.8(8)
  • Description: Background 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. Design In the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among 57,053 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 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. 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 not be fully compensated by a higher intake of vitamin C rich food.
  • Identifier: E-ISSN: 1932-6203 ; DOI: 10.1371/journal.pone.0070421 ; PMCID: 3749152 ; PMID: 23990905