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

Christine Dalgård,Claus Dethlefsen,Anne Tjønneland,Lene Christiansen,Ulla Vogel,Kim Overvad,Vincenzo Lionetti

doi:10.1371/journal.pone.0070421

Abstract

BackgroundVitamin 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.DesignIn the Danish Diet, Cancer and Health cohort study, we performed a case-cohort study among 57,053 subjects aged 50–64 years.ResultsDuring 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.ConclusionGenetic 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.

Highlights

Acute coronary syndrome (ACS) is still among the leading causes of mortality in Denmark as well as internationally [1] despite recent declines in mortality rates
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
For the rs1776964 polymorphism, we found a higher risk among TT-homozygous women with higher than median vitamin C intake compared with the CC genotype and low vitamin C intake

Summary

Introduction

Acute coronary syndrome (ACS) is still among the leading causes of mortality in Denmark as well as internationally [1] despite recent declines in mortality rates. 90% of the population attributable risk can be related to 9 specific risk factors including low intake of fruit and vegetables [3] that have consistently been associated with risk of cardiovascular disease [4]. One of the main cardioprotective factors in fruits and vegetables may be vitamin C and numerous mechanisms have already been identified including anti-oxidative effects and beneficial effects on endothelial function. 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. 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

Results

Conclusion