Journal
AMERICAN JOURNAL OF CLINICAL NUTRITION
Volume 92, Issue 2, Pages 375-382Publisher
ELSEVIER SCIENCE INC
DOI: 10.3945/ajcn.2010.29438
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Funding
- MRC CAiTE Centre [G0600705]
- MRC [G0601625, G9900686]
- BHF [FS/05/095/19937, PG97012, PG97027, FS05/125]
- Department of Health Policy Research Division
- Wellcome Trust [051187/Z/97/A]
- NHS
- British Heart Foundation Research Group
- Cancer Research Campaign, the Medical Research Council
- Stroke Association
- Department of Health
- Europe Against Cancer Programme Commission of the European Union
- Ministry of Agriculture, Fisheries and Food
- British Heart Foundation [RG/08/013/25942] Funding Source: researchfish
- Medical Research Council [MC_U106179471, G0601625, G0600705, MC_UP_A100_1003] Funding Source: researchfish
- MRC [MC_UP_A100_1003, G0601625, G0600705] Funding Source: UKRI
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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 mu mol/L; 95% CI: -0.49, -7.81 mu mol/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 mu mol/L (95% CI: -8.23, -3.73 mu mol/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. Am J Clin Nutr 2010; 92: 375-82.
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