Effect of RBP4 gene variants on circulating RBP4 concentration and type 2 diabetes in a Chinese population.
OBJECTIVE
Retinol binding protein 4 (RBP4) is a newly discovered adipokine, which plays a role in insulin resistance and obesity. The aim of this study was to determine the relationship between genetic variants of the RBP4 gene, circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism in the Chinese population.


METHODS
We sequenced exons and the putative promoter region to identify single nucleotide polymorphisms (SNPs) in the RBP4 gene in 32 Chinese subjects. Additional SNPs were selected from a public database to increase marker density. Taking account of the pairwise linkage disequilibrium and minor allele frequencies, a subset of SNPs was further genotyped in 255 Type 2 diabetic patients and 372 normal control subjects. Circulating RBP4 concentrations and phenotypes related to glucose and lipid metabolism were measured.


RESULTS
Ten SNPs were identified and five were further genotyped in the full sample. No individual SNP was significantly associated with Type 2 diabetes, but a rare haplotype CAA formed by +5388 C>T, +8201 T>A and +8204 T>A was more frequent in diabetic patients (P = 0.0343, empirical P = 0.0659 on 10 000 permutations). In both groups, non-coding SNPs were associated with circulating RBP4 concentrations (P < 0.05). In the normal control subjects, the SNP +5388 C>T was associated with serum C-peptide levels both fasting and 2 h after an oral glucose tolerance test (P = 0.0162 and P = 0.0075, respectively).


CONCLUSIONS
Our findings suggest that genetic variants in the RBP4 gene may be associated with circulating RBP4 concentration and phenotypes related to glucose metabolism.
Hu
C
C
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Jia
W
W
Zhang
R
R
Wang
C
C
Lu
J
J
Wu
H
H
Fang
Q
Q
Ma
X
X
Xiang
K
K
D000273:Adipose Tissue; D000328:Adult; D000704:Analysis of Variance; D044466:Asian People / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006239:Haplotypes; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics*; D000078790:Insulin Secretion; D015810:Linkage Disequilibrium; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics* / Q000378:metabolism
D007328:Insulin; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma