循环 25-羟维生素 D、IRS1 变异 rs2943641 和胰岛素抵抗：在不同祖源的 4 个人群中复制基因-营养相互作用。
Circulating 25-hydroxyvitamin D, IRS1 variant rs2943641, and insulin resistance: replication of a gene-nutrient interaction in 4 populations of different ancestries.
机构信息
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA;
出版信息
Clin Chem. 2014 Jan;60(1):186-96. doi: 10.1373/clinchem.2013.215251. Epub 2013 Nov 19.
BACKGROUND
Associations of either insulin receptor substrate 1 (IRS1) variants or circulating 25-hydroxyvitamin D [25(OH)D] with type 2 diabetes (T2D) and insulin resistance (IR) are inconsistent. This study sought to determine whether circulating 25(OH)D modulates the association of a potentially functional variant at IRS1 (rs2943641) with insulin resistance.
METHOD
Interaction between IRS1 rs2943641 and circulating 25(OH)D on homeostasis model assessment for IR (HOMA-IR) was examined in the Boston Puerto Rican Health Study (BPRHS) (n = 1144). Replication was performed in the African-American (n = 1126), non-Hispanic white (n = 1967), and Hispanic (n = 1241) populations of the Multi-Ethnic Study of Atherosclerosis (MESA) with genotypes of 3 IRS1 variants, rs2972144, rs1515104, and rs2673142, which are tag single nucleotide polymorphisms (SNPs) and in strong linkage disequilibrium with rs2943641.
RESULTS
Higher circulating 25(OH)D was associated with lower risk of T2D and IR in BPRHS women homozygous for minor allele rs2943641T. Consistently, in each of 3 MESA populations, HOMA-IR and insulin decreased more evidently with higher circulating 25(OH)D in women of the rs2943641TT genotype than in carriers of the major allele (rs2943641C). Metaanalysis indicated significant and consistent interactions between circulating 25(OH)D and IRS1 variants on HOMA-IR (log transformed) [pooled β = -0.008, 95% CI: -0.016 to -0.001, P interaction = 0.004] and insulin (log transformed) (pooled β = -0.006, 95% CI: -0.011 to -0.002, P interaction = 0.023) in 3065 women of the 4 populations.
CONCLUSIONS
Participants with different genotypes of IRS1 rs2943641 exhibit differential benefit from high circulating 25(OH)D for the reduction of insulin resistance and T2D risk. This gene-nutrient interaction, which appears to be limited to women, warrants further examination in randomized controlled trials of vitamin D supplementation.
背景
胰岛素受体底物 1（IRS1）变体或循环 25-羟维生素 D [25（OH）D]与 2 型糖尿病（T2D）和胰岛素抵抗（IR）的关联不一致。本研究旨在确定循环 25（OH）D 是否调节 IRS1 中潜在功能变体（rs2943641）与胰岛素抵抗之间的关联。
方法
在波士顿波多黎各健康研究（BPRHS）中（n = 1144），检查 IRS1 rs2943641 与循环 25（OH）D 之间的相互作用对内稳态模型评估的胰岛素抵抗（HOMA-IR）。在非洲裔美国人（n = 1126）、非西班牙裔白人（n = 1967）和西班牙裔（n = 1241）人群中进行了复制多民族动脉粥样硬化研究（MESA），基因型为 3 IRS1 变体 rs2972144、rs1515104 和 rs2673142，这些是标签单核苷酸多态性（SNP），与 rs2943641 紧密连锁。
结果
在 BPRHS 女性中，循环 25（OH）D 水平较高与 T2D 和 IR 风险降低相关，且该女性为 minor allele rs2943641T 的纯合子。同样，在 MESA 的 3 个人群中，与携带主要等位基因（rs2943641C）的女性相比，rs2943641TT 基因型的女性循环 25（OH）D 水平越高，HOMA-IR 和胰岛素的降低更为明显。Meta 分析表明，循环 25（OH）D 与 IRS1 变体之间存在显著且一致的相互作用，对 HOMA-IR（对数转换）[汇总 β = -0.008，95%CI：-0.016 至 -0.001，P 交互 = 0.004]和胰岛素（对数转换）（汇总 β = -0.006，95%CI：-0.011 至 -0.002，P 交互 = 0.023）有影响，4 个人群中共有 3065 名女性。
结论
IRS1 rs2943641 不同基因型的参与者从高循环 25（OH）D 中获得了不同的益处，可降低胰岛素抵抗和 T2D 风险。这种似乎仅限于女性的基因-营养相互作用，值得在维生素 D 补充的随机对照试验中进一步研究。
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