Gene-Environmental Interaction between Cyplal, Cyplbl, and Cyp2b6 Polymorphisms and Vitamin D on Insulin Resistance: A Panel Study of an Elderly Population

摘要

Objective: As evidence on effect of vitamin D deficiency over insulin resistance(IR) or diabetes mellitus is accumulating, investigation for any gene-environmental contribution to disease development should be accompanied. We thus evaluated the influence of certain cytochrome P450 polymorphisms and vitamin D levels on IR. Methods: Glucose, insulin as well as 25-hydroxyvitamin D levels [25(OH)D] levels from serum, and CYP1A1, CYP1B1, CYP2B6 single-nucleotide polymorphisms (SNPs) from lymphocyte DNA were measure in 535 Seoul residents over 60 years old. Homeostasis model assessment for insulin resistance(HOMA-IR) was calculated, and repeated measure analyses were used to determine the statistical association. Results: Relationship between 25(OH)D insulin (3 = -0.84, P = 0.02) or HOMA-IR (3 = -0.26, P = 0.04) was inversely significant, and influence of CYP1A1 (rsl048943), CYP1B1 (rsl62561, rs2551188) and CYP2B6 (rs3745274) SNPs on IR was found across different genotypes. Estimated effect of 25(OH)D levels on IR in the group with higher risky genotype scores of selected SNPs was greater than the group with lower genotype score. Interaction effect between vitamin D levels and genotype variations was also observed (P-interaction <.05 for both insulin and HOMA-IR). Conclusion: Genetic variations in CYP1A1, CYP1B1 and CYP2B6 and the serum levels of 25(OH)D showed interactive effect on IR.