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


METHODS
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).


CONCLUSIONS
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.
Ye
W Z
WZ
INSERM Unité 342, Hôpital Saint-Vincent de Paul, Paris, France.
Reis
A F
AF
Dubois-Laforgue
D
D
Bellanné-Chantelot
C
C
Timsit
J
J
Velho
G
G
D017668:Age of Onset; D000368:Aged; D015992:Body Mass Index; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics*
D018167:Receptors, Calcitriol; D004247:DNA