Background: 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.

Objective: To investigate the relationship of DBP polymorphisms and obesity in Caucasian nuclear families.

Design: 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.

Results: SNP2 (rs17467825) and its corresponding haplotype GAA (frequency 0.270) in block1 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.

Conclusion: 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.