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

NJ Timpson, NG Forouhi, M-J Brion, RM Harbord, DG Cook, P Johnson, A McConnachie, RW Morris, S Rodríguez, J Luan, S Ebrahim, S Padmanabhan, G Watt, KR Bruckdorfer, NJ Wareham, PH Whincup, S Chanock, N Sattar, D Lawlor, G Davey Smith

Research output: Contribution to journalArticle (Academic Journal)peer-review

72 Citations (Scopus)

Abstract

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.

DESIGN: 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.
Translated title of the contributionGenetic 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
Original languageEnglish
Pages (from-to)375 - 382
Number of pages8
JournalAmerican Journal of Clinical Nutrition
Volume92
Issue number2
DOIs
Publication statusPublished - Aug 2010

Keywords

  • Adult
  • Aged
  • Ascorbic Acid
  • Cohort Studies
  • Female
  • Genetics, Population
  • Genotype
  • Humans
  • Linear Models
  • Male
  • Middle Aged
  • Organic Anion Transporters, Sodium-Dependent
  • Polymorphism, Single Nucleotide
  • Sodium-Coupled Vitamin C Transporters
  • Symporters

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