Genetic variation at the SLC23A1 locus is associated with circulating concentrations of L-ascorbic acid (vitamin C): evidence from 5 independent studies with >15,000 participants.
The American Journal of Clinical Nutrition 2010 ; 92: 375-82.
Timpson NJ, Forouhi NG, Brion MJ, Harbord RM, Cook DG, Johnson P, McConnachie A, Morris RW, Rodriguez S, Luan J, Ebrahim S, Padmanabhan S, Watt G, Bruckdorfer KR, Wareham NJ, Whincup PH, Chanock S, Sattar N, Lawlor DA, and Davey Smith G
DOI : 10.3945/ajcn.2010.29438
PubMed ID : 20519558
PMCID : PMC3605792
L-ascorbic acid is an essential part of the human diet and has been associated with a wide range of chronic complex diseases, including cardiovascular outcomes. To date, there are no confirmed genetic correlates of circulating concentrations of L-ascorbic acid.
We aimed to confirm the existence of an association between common variation at the SLC23A1 gene locus and circulating concentrations of L-ascorbic acid.
We used a 2-stage design, which included a discovery cohort (the British Women's Heart and Health Study), a series of follow-up cohorts, and meta-analysis (totaling 15,087 participants) to assess the relation between variation at SLC23A1 and circulating concentrations of L-ascorbic acid.
In the discovery cohort, variation at rs33972313 was associated with a reduction in circulating concentrations of L-ascorbic acid (-4.15 micromol/L; 95% CI: -0.49, -7.81 micromol/L; P = 0.03 reduction per minor allele). Pooled analysis of the relation between rs33972313 and circulating L-ascorbic acid across all studies confirmed this and showed that each additional rare allele was associated with a reduction in circulating concentrations of L-ascorbic acid of -5.98 micromol/L (95% CI: -8.23, -3.73 micromol/L; P = 2.0 x 10(-7) per minor allele).
A genetic variant (rs33972313) in the SLC23A1 vitamin C active transporter locus was identified that is reliably associated with circulating concentrations of L-ascorbic acid in the general population. This finding has implications more generally for the epidemiologic investigation of relations between circulating L-ascorbic acid and health outcomes.