Vitamin D receptor gene polymorphisms are associated with obesity in type 2 diabetic subjects with early age of onset

INSERM Unite 342, Hopital Saint-Vincent de Paul, Paris, France.

OBJECTIVE: Allelic variations in the vitamin D receptor (VDR) gene were reported to modulate insulin secretion in response to glucose. VDR was investigated as a candidate gene for type 2 diabetes mellitus (T2DM). METHOD: Four single nucleotide polymorphisms (SNPs) in intron 8 (BsmI, Tru9I, ApaI) and exon 9 (TaqI) of the VDR gene were examined in 309 unrelated French subjects with T2DM and 143 controls. RESULTS: The distribution of alleles and genotypes of the four SNPs was similar in patients and controls. However, in patients whose age at diagnosis of diabetes was < or =45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) (31.7+/-6.7 kg/m2, P=0.0058) and an increased prevalence of obesity (81%, P=0.005) with respect to heterozygous subjects (27.9+/-5.0 kg/m2; 46%) or homozygous subjects for the t-allele (27.7+/-5.0 kg/m2; 52%). Similar results were observed for homozygous subjects for the b-allele of the BsmI SNP. Logistic regression analysis demonstrated that TT homozygosity was independently associated with obesity in these subjects (odds ratio, 4.64; 95% confidence interval (CI), 1.64-14.76; P=0.0056). CONCLUSION: VDR is not a major gene for T2DM in French Caucasians. However, polymorphisms in the VDR gene are associated with the susceptibility to obesity in subjects with early-onset T2DM. The pathophysiological mechanisms of these associations remain unexplained, but they could be related to a direct effect of vitamin D in adypocyte differentiation and metabolism, or to an indirect effect by modulation of insulin secretion.