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.
Timpson
Nicholas J
NJ
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
Forouhi
Nita G
NG
Brion
Marie-Jo
MJ
Harbord
Roger M
RM
Cook
Derek G
DG
Johnson
Paul
P
McConnachie
Alex
A
Morris
Richard W
RW
Rodriguez
Santiago
S
Luan
Jian'an
J
Ebrahim
Shah
S
Padmanabhan
Sandosh
S
Watt
Graham
G
Bruckdorfer
K Richard
KR
Wareham
Nicholas J
NJ
Whincup
Peter H
PH
Chanock
Steve
S
Sattar
Naveed
N
Lawlor
Debbie A
DA
Davey Smith
George
G
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