Circulating 25-Hydroxyvitamin D, IRS1 Variant rs2943641, and Insulin Resistance: Replication of a Gene-Nutrient Interaction in 4 Populations of Different Ancestries.

Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA;
Clinical Chemistry (Impact Factor: 7.15). 11/2013; DOI: 10.1373/clinchem.2013.215251
Source: PubMed

ABSTRACT 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). Meta-analysis indicated significant and consistent interactions between circulating 25(OH)D and IRS1 variants on HOMA-IR (log transformed) [pooled β = -0.008, 95% confidence interval (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.

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    ABSTRACT: In the study of longevity, increasing importance is being placed on the concept of healthy ageing rather than considering the total number of years lived. Although the concept of healthy lifespan needs to be defined better, we know that cardiovascular diseases (CVDs) are the main age-related diseases. Thus, controlling risk factors will contribute to reducing their incidence, leading to healthy lifespan. CVDs are complex diseases influenced by numerous genetic and environmental factors. Numerous gene variants that are associated with a greater or lesser risk of the different types of CVD and of intermediate phenotypes (i.e., hypercholesterolemia, hypertension, diabetes) have been successfully identified. However, despite the close link between ageing and CVD, studies analyzing the genes related to human longevity have not obtained consistent results and there has been little coincidence in the genes identified in both fields. The APOE gene stands out as an exception, given that it has been identified as being relevant in CVD and longevity. This review analyzes the genomic and epigenomic factors that may contribute to this, ranging from identifying longevity genes in model organisms to the importance of gene-diet interactions (outstanding among which is the case of the TCF7L2 gene).
    Ageing Research Reviews. 01/2014;


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May 27, 2014