Analysis Of Adiponectin Gene Polymorphisms And Their Effect On The Response To Rosiglitazone In Chinese Patients With Type 2 Diabetes

AIMS: In this study, we were to investigate the distribution frequency of adiponectin of single nucleotide polymorphisms (SNP) and its haplotypes and determine effect of genetic polymorphisms of adiponectin on the therapeutical efficacy of rosiglitazone in patients with type 2 diabetes(T2D).METHODS: A totle of 255 T2D patients and 120 health volunteers were selected to genotype at -11377(C/G) and +45(T/G) polymorphisms of adiponectin gene by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Samples were randomly selected to direct sequencing to identify the results of PCR-RFLP. 42 T2D patients were selected to administere orally 4mg rosiglitazone daily for 12 consecutive weeks. Plasma concentration of FPG, PPG, HbAlc as well as serum concentration of FINS and PINS in all subjects were determined at 0 and 12th weekend. The frequency of haplotypes was calculated using phase sofeware haplotypes estimation. Statistical analyses include one-way ANOVA, paird t test ,Chi-square (?~2) analysis and non-parametric test.RESULTS: The distribute characters of both alleles were accorded with Hardy-Weinberg equilibrium. In T2D, the allele frequencies for-11377(C/G) and +45(T/G) were 28.8% and 28.0% respectively. There were significant different in allele frequency of-11377(C/G) between health volunteers and T2D patients.However, in subjects with -11377(C/G) genotypes, there was a significant lower in the serum adiponectin concentration (P＜0.001) and higher in the FINS(P＜0.05 ) and HOMA-IR(P＜0.05 ) for the G allele gene than CC genotype in T2D patients (P＜0.05). In subjects with 45(T/G) genotypes, there was a marked higher in the waist-to-hip ratio in patients with the TT genotype than those with the others genotype in T2D patients (P＜ 0.05). To haplotype analysis, the level of FPG(P＜0.05), PPG(P＜0.01), FINS(P＜0.05) and LDL-c(P＜0.05) were higher in those with CGTT diplotype than those with the other diplotypes (P＜0.05). Finally, we observed the effect of C-11377G and T45G polymorphisms on the therapeutic efficacy of rosiglitazone in patients with T2D. In subjects with -11377 genotypes, the degree of the decrease in the FPG (P＜0.001), PPG (P＜0.05) and HOMA-IR (P＜0.05) level were significant higher in those with the CC genotype than those with the other genotypes.However, the degree of the increase in the serum adiponectin concentration(P＜0.01) was significantly higher in those with the CC genotype than those with the other genotypes.In subjects with 45 genotypes, the degree of the increase in the serum adiponectin concentration was significantly s in those with the G allele than those with the CC genotype (P＜0.05). To haplotype analysis, the degree of the reduction in the FPG FPG (P＜0.001), PPG (P＜0.05) and HOMA-IR (P＜0.05) level was smaller for the CGTT diplotype than for the other diplotypes. In addition, the degree of the increase in the adiponectin concentration(P＜0.001) was significant smaller in the subjects with CGTT diplotype than the subjects with the other diplotypes.CONCLUSION: -11377(C/G) and +45(T/G) are common polymorphisms of adiponectin gene in Chinese population. There was an associated between polymorphism of adiponectin gene -11377(C/G) and CGTT diplotype with the pathogenesis of T2D. The -11377G allele and CGTT diplotype might be a risk factor for the development of T2D. This study suggests that patients with CC genotype at locus -11377 are sensitive to the therapeutical efficacy of rosiglitazone in patients with type 2 diabetes. However, patients with CGTT diplotype are unlikely to respond to the rosiglitazone.These data suggest that genetic variations in the adiponectin gene could affect the therapeutic efficacy and improve the insulin resistance and increase the level of adiponectin in patients with type 2 diabetic patients.