Timpson Nicholas J, Forouhi Nita G, Brion Marie-Jo, Harbord Roger M, Cook Derek G, Johnson Paul, McConnachie Alex, Morris Richard W, Rodriguez Santiago, Luan Jian'an, Ebrahim Shah, Padmanabhan Sandosh, Watt Graham, Bruckdorfer K Richard, Wareham Nicholas J, Whincup Peter H, Chanock Steve, Sattar Naveed, Lawlor Debbie A, Davey Smith George
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.
Am J Clin Nutr. 2010 Aug;92(2):375-82. doi: 10.3945/ajcn.2010.29438. Epub 2010 Jun 2.
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.
We aimed to confirm the existence of an association between common variation at the SLC23A1 gene locus and circulating concentrations of L-ascorbic acid.
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.
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).
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.
L-抗坏血酸是人类饮食的重要组成部分，与多种慢性复杂疾病相关，包括心血管疾病。迄今为止，尚未证实L-抗坏血酸循环浓度的基因相关性。
我们旨在证实SLC23A1基因座的常见变异与L-抗坏血酸循环浓度之间存在关联。
我们采用两阶段设计，包括一个发现队列（英国女性心脏与健康研究）、一系列随访队列以及荟萃分析（总计15087名参与者），以评估SLC23A1变异与L-抗坏血酸循环浓度之间的关系。
在发现队列中，rs33972313变异与L-抗坏血酸循环浓度降低相关（-4.15微摩尔/升；95%置信区间：-0.49，-7.81微摩尔/升；每个次要等位基因降低P = 0.03）。对所有研究中rs33972313与循环L-抗坏血酸之间关系的汇总分析证实了这一点，并表明每增加一个罕见等位基因与L-抗坏血酸循环浓度降低-5.98微摩尔/升相关（95%置信区间：-8.23，-3.73微摩尔/升；每个次要等位基因P = 2.0×10⁻⁷）。
在SLC23A1维生素C活性转运基因座中鉴定出一种基因变异（rs33972313），该变异与普通人群中L-抗坏血酸的循环浓度可靠相关。这一发现对循环L-抗坏血酸与健康结果之间关系的流行病学调查具有更广泛的意义。
