The Association of Functional Single Nucleotide Polymorphisms of the RBP4 Gene with Gene Expression and Insulin Resistance Risk

Aims/Introduction: The RBP4 level has been found to correlate positively with risk of insulin resistance and type 2 diabetes. However, the exact mechanism linking RBP4 with metabolic disorders is not clear. In presented study the associations of two single nucleotide polymorphisms located in promoter region of the RBP4 gene rs3758538 (-1265A>C) and rs3758539 (-803 G>A) with insulin resistance risk, RBP4 mRNA level and biochemical parameters were analyzed. Material and methods: Two polymorphisms were genotyped by multiplex minisequencing with the use of ABI PRISM® SNaPshot Multiplex Kit. RBP4 gene expression analysis was done by Relative Real-Time PCR and normalized to β-actin and GUS-β genes. Insulin and cytokines were measured using commercial ELISA kits. Results: IR patients were characterized by increased RBP4 mRNA level in adipose tissue comparing to IS patients and control subjects, what correlated positively with insulin resistance. Polymorphism rs3758539 showed no differences in genotype frequencies between tested groups. The rs3758538 displayed higher number of C allele within type 2 diabetes patients. There was no relationship between genotype and RBP4 gene expression level. Furthermore, no relationship of investigated SNPs with insulin resistant phenotype has been noticed. Conclusions: Present results link the RBP4 gene expression level with insulin resistance pathogenesis. However, there is lack of association between analyzed SNPs with insulin resistant phenotype, RBP4 gene expression level and inflammatory state.