Association analysis of vitamin D-binding protein gene polymorphisms with variations of obesity-related traits in Caucasian nuclear families.

Abstract

Vitamin D-binding protein (DBP) gene is well known for its function on glucose and vitamin D metabolism in human populations. Previous studies suggested that the in vivo DBP level may play a role in the etiology of obesity. However, few studies explored the contribution of DBP gene to the variance of obesity phenotypes. To investigate the relationship of DBP polymorphisms and obesity in Caucasian nuclear families. We genotyped 14 single-nucleotide polymorphisms (SNPs) located in and around the DBP gene in 1873 Caucasian subjects from 405 nuclear families. Three obesity-related quantitative phenotypes were investigated, including body mass index (BMI), fat mass and percentage of fat mass (PFM). Single SNPs and haplotypes (three blocks) were tested by family-based association using the FBAT software. SNP2 (rs17467825) and its corresponding haplotype GAA (frequency 0.270) in block 1 showed strongest associations with PFM (P=0.0011 and 0.0023, respectively). In multivariate test significant association was also observed for SNP2 with fat mass&BMI&PFM (P=0.0098). Subsequent sex-stratified analyses demonstrated nominal association for SNP2 and haplotype GAA with PFM in the female subgroup. Polymorphisms of DBP gene were significantly association with human PFM, especially in female, suggesting the importance of DBP gene in the pathogenesis of human obesity.