Document Detail


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.
MedLine Citation:
PMID:  20519558     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nicholas J Timpson; Nita G Forouhi; Marie-Jo Brion; Roger M Harbord; Derek G Cook; Paul Johnson; Alex McConnachie; Richard W Morris; Santiago Rodriguez; Jian'an Luan; Shah Ebrahim; Sandosh Padmanabhan; Graham Watt; K Richard Bruckdorfer; Nicholas J Wareham; Peter H Whincup; Steve Chanock; Naveed Sattar; Debbie A Lawlor; George Davey Smith
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Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't     Date:  2010-06-02
Journal Detail:
Title:  The American journal of clinical nutrition     Volume:  92     ISSN:  1938-3207     ISO Abbreviation:  Am. J. Clin. Nutr.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-07-21     Completed Date:  2010-08-12     Revised Date:  2011-01-21    
Medline Journal Info:
Nlm Unique ID:  0376027     Medline TA:  Am J Clin Nutr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  375-82     Citation Subset:  AIM; IM    
Affiliation:
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
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Ascorbic Acid / blood*
Cohort Studies
Female
Genetics, Population
Genotype
Humans
Linear Models
Male
Middle Aged
Organic Anion Transporters, Sodium-Dependent / genetics*
Polymorphism, Single Nucleotide*
Symporters / genetics*
Grant Support
ID/Acronym/Agency:
051187/Z/97/A//Wellcome Trust; FS/05/095/19937//British Heart Foundation; FS05/125//British Heart Foundation; G0600705//Medical Research Council; G0601625//Medical Research Council; G9900686//Medical Research Council; PG97012//British Heart Foundation; PG97027//British Heart Foundation; //Department of Health
Chemical
Reg. No./Substance:
0/Organic Anion Transporters, Sodium-Dependent; 0/Symporters; 0/sodium-dependent vitamin C transporter; 50-81-7/Ascorbic Acid
Comments/Corrections
Comment In:
Am J Clin Nutr. 2010 Aug;92(2):271-2   [PMID:  20592130 ]

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