Association of vitamin D receptor gene polymorphisms with insulin resistance and response to vitamin D.

The objectives of the study were to determine associations between single nucleotide polymorphisms (SNPs) of the vitamin D receptor (VDR) gene and insulin resistance and the effects of these SNPs on changes in insulin sensitivity in response to vitamin D supplementation. The research described here was an extension of the Surya study. Genotyping of the Cdx-2, FokI, BsmI, ApaI, and TaqI SNPs was carried out on 239 South Asian women in New Zealand using polymerase chain reaction-based techniques. Associations of these genotypes and 3' end haplotypes with insulin resistance were determined using multiple regression analysis. Associations between SNP genotypes and responses in insulin sensitivity to vitamin D supplementation (4000 IU vitamin D(3) per day) were also determined for a subset (81) of these women. BsmI BB, ApaI AA, and TaqI tt genotypes were significantly associated with lower insulin resistance compared with BsmI bb, ApaI aa, and TaqI TT, respectively, in the cohort of 239 women. Furthermore, homozygosity of the haplotypes baT and BAt was associated with higher and lower insulin resistance, respectively, compared with no copies of their respective alleles. Of the 81 subjects who were supplemented with vitamin D, women with the FokI Ff genotype showed a significantly greater improvement in insulin sensitivity (increase of 29.4 [2.9, 38.1]) compared with women with the FokI FF genotype (increase of 2.3 [-11.5, 10.1]). This study has highlighted the association of vitamin D responsiveness and insulin resistance with VDR gene polymorphisms. This is the first study to determine associations between all three. Genotyping of the VDR gene may provide a predictive measure for insulin resistance in response to vitamin D intervention.