title: Variation in the sodium-dependent vitamin C transporter 2 gene is associated with risk of acute coronary syndrome among women.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Christine
authors.initials: C
authors.lastname: Dalgård
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: Claus
authors.initials: C
authors.lastname: Dethlefsen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics*; D001205:Ascorbic Acid / Q000378:metabolism; D015331:Cohort Studies; D004032:Diet; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D012306:Risk; D060347:Sodium-Coupled Vitamin C Transporters / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D001205:Ascorbic Acid