Impact Of RBP-4 Genetic Polymorphisms On The Response To Rosiglitazone In Chinese Patients With Type 2 Diabetes

Aims:To explore the genetic variation in retinol binding protein 4(RBP4) and to study the role of RBP4 -803G/A and -179T/G polymorphisms in the pathogenesis of type 2 diabetes.To examine the effects of RBP4 gene polymorphisms on the response to rosiglitazone in patients with type 2 diabetes mellitus and to provide evidence for individual treatment..METHODS:245 type 2 diabetes patients and 122 healthy subjects were selected to genotyped at-803(G/A)and-179(T/G)polymorphisms of RBP4 gene by the technique of polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).Samples were randomly selected to direct sequencing to identify the results of PCR-RFLP.42 T2DM patients were selected to orally administered with 4rag rosiglitazone daily for 12 weeks. Plasma FPG,PPG,HbAle and serum FINS,PINS levels were determined at 0 and 12th weekend.The frequency of haplotypes was calculated using phase sofeware haplotypes estimation.Statistical analyses include two-sample t-test, x~2 analysis and non-parametric test.RESULTS:The allelie frequencies of-803G/A and -179T/G were 11.89% and 13.11%in healthy subjects,respectively,In type 2 diabetes,the allele frequencies for-803G/A and -179T/G were 15.91%and 16.53%respectively. but no individual SNP was significantly associated with Type 2 diabetes.The distributions of both alleles were accorded with Hardy-Weinberg equilibrium. we observed a significant linkage disequilibrium between -803G/A locus and -179T/G loens(|D'|=0.688,r~2 =0.17).No haplotypes was more frequent in the case subjects than in the control subjects,there were significant differences in HOMA-IR,TG and LDL-c between -803 GG genotype and -803 GA+AA genotypes(P＜0.05;P＜0.01;P＜0.01).However,in-179T/G genotyped patients with T2D,there were significant differences in waist-hip ratio,FPG,FINS between TT genotype and TG+GG genotypes(P＜0.05;P＜0.05 and P＜0.05).After 12 weeks of rosiglitazone treatment,patients with-803 GG genotype had higher differential values(DV)of FPG(p=0.03),FINS(p=0.01) and HOMA-IR(p=0.04)than those in GA+AA genotype, respectively.Patients with -179 TG+ GG genotype had higher differential value of HbAlc than that in TT genotype(p=0.03).CONCLUSION:-803(G/A)and-179(T/G)are common polymorphisms of RBP4 gene in Chinese population.These data suggest that genetic variations in the RBP4 gene can affect the clinical features related to glucose and lipid metabolism in type 2 diabetes patients.It is the first time to investigate the influence of RBP4 gene in therapeutic efficacy of rosiglitazone among Chinese type 2 diabetes patients.T2D patients with -803GG homozygote genotype were good responders to rosiglitazone monotherapy.