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.
BACKGROUND
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.


OBJECTIVE
We aimed to confirm the existence of an association between common variation at the SLC23A1 gene locus and circulating concentrations of L-ascorbic acid.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Medical Research Council Centre for Causal Analyses in Translational Epidemiology, University of Bristol, Department of Social Medicine, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, United Kingdom. n.j.timpson@bris.ac.uk
Nicholas J
NJ
Timpson
Nita G
NG
Forouhi
Marie-Jo
MJ
Brion
Roger M
RM
Harbord
Derek G
DG
Cook
Paul
P
Johnson
Alex
A
McConnachie
Richard W
RW
Morris
Santiago
S
Rodriguez
Jian'an
J
Luan
Shah
S
Ebrahim
Sandosh
S
Padmanabhan
Graham
G
Watt
K Richard
KR
Bruckdorfer
Nicholas J
NJ
Wareham
Peter H
PH
Whincup
Steve
S
Chanock
Naveed
N
Sattar
Debbie A
DA
Lawlor
George
G
Davey Smith
D000328:Adult; D000368:Aged; D001205:Ascorbic Acid / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters / Q000235:genetics*
D029363:Organic Anion Transporters, Sodium-Dependent; C555162:SLC23A1 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D001205:Ascorbic Acid