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

Abstract

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 #45 years, homozygous subjects for the T-allele of the TaqI SNP had a higher body mass index (BMI) 31X7^6X7 kgam 2 Y P 0X0058 and an increased prevalence of obesity (81%, P 0X005 with respect to heterozygous subjects 27X95 X0 kgam 2 ; 46%) or homozygous subjects for the t-allele 27X7^5X0 kgam 2 ; 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% con®dence interval (CI), 1.64±14.76; P 0X0056. 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.

Taq I polymorphism of the vitamin D receptor and risk of severe diabetic retinopathy

“…Furthermore, non-glycaemic factors could be important in the progression of diabetic complications [3,23]. Even though our study did not include non-diabetic control subjects, the distribution of Taq I polymorphism among our cohort was similar to that observed in other French cohorts [16,29], thus excluding a selection bias.…”

Polimorfizmy genu receptora witaminy D (TaqI oraz ApaI) oraz cyrkulacja osteokalcyny u pacjentów chorujących na cukrzycę typu 2 i osób zdrowych

“…Previous studies have reported the association between TT genotype of TaqI polymorphism and obesity. This genotype accounted for a difference of about 9 kg of body weight in that group of subjects [15]. The pathophysiological mechanisms of this association remain unexplained.…”

1α, 25-Dihydroxyvitamin D and corticosteroid regulate adipocyte nuclear vitamin D receptor

“…Polymorphisms in the nVDR are associated with obesity susceptibility in humans, 21,22 and several lines of evidence demonstrate alterations in the vitamin D-endocrine system in obese humans. 23,24 We have demonstrated that 1a, 25-dihydroxyvitamin D suppresses uncoupling protein 2 expression in human adipocytes, 6 and this effect appears to be mediated by the adipocyte nVDR, as 1b, 25-dihydroxyvitamin D was unable to block this effect, whereas nVDR knockout successfully inhibited it.…”