Association of RBP4 Gene Variants and Serum HDL Cholesterol Levels in the Newfoundland Population

Retinol-binding protein 4 (RBP4) is a novel adipokine that likely contributes to systemic insulin resistance and dyslipidemia. The role of genetic variations in RBP4 on phenotypes of glucose and lipid metabolism is not clear in humans. The purpose of this study was to examine five single-nucleotide polymorphisms (SNPs) in the RBP4 gene to determine their relationship with markers of insulin resistance and serum lipids in the CODING Study. The CODING Study consists of 1,836 subjects recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA(IR)), HOMA for beta cell function (HOMA(beta)), total cholesterol (Chol), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were determined after a 12-h fast. Five SNPs within RBP4 (rs3758539, G/A 5' flanking region; rs61461737, A/G intron; rs10882280, C/A intron; rs11187545, A/G intron; and rs12265684, C/G intron) were genotyped using TaqMan validated or functionally tested SNP genotyping assays. After correcting for multiple testing, we observed a significant association between the minor allele of two noncoding SNPs (rs10882280 and rs11187545) and higher serum HDL-C (P = 0.043 and 0.042, respectively). No significant associations were observed with any other parameter related to lipid metabolism. We also found no significant association between any variant sites and markers of insulin resistance. Our results suggest that genetic variations in RBP4 may play a role in the differences in serum HDL-C levels in the NL population.