| Aims: Adipose tissue can secret leptin and TNF-α, which contributes to glucosehomeostasis,insulin resistance and the effect of glucose decrease of rosiglitazone. Thepresent study aimed at investigating the association between leptin G-2548A, TNF-αG-308A polymorphisms and the pathogenesis of type 2 diabetes as well as their effects onrosiglitazone response in patients with type 2 diabetes.Methods: Genotyping were determined using the PCR-RFLP in 245 patients withtype 2 daibetes (132 males and 113 females) and 122 healthy volunteers (68 males and 54females). Leptin concentration was determined by ABC-ELISA. 42 type 2 diabetes wereselected to orally administered with 4mg rosiglitazone daily for 12 consecutive weeks.Plasma concentration ofFBG, PBG, HbAlc and serum Fins, Pins level were determined at0 and 12th weekend after administration. Statistical analyses were performed by one-wayANOVA,Wilcoxon rank sum test,paired t-test and Chi-square(x~2).Results: The two polymorphisms of leptin and TNF-αgenes were in Hardy-Weinbergequilibrium. The allelic frequency of-2548A (leptin) in patients with type 2 diabetes andhealth control were 73.5% and 70.1%, respectively. No significant difference was observedbetween two groups (P＞0.05). Further study showed that the variation of-2548A allelewas associated with BMI,serum leptin levels and FBG in patients with type 2 diabetes.Patients with G allele of leptin (G-2548A) had smaller BMI,lower level of serum leptinconcertration and bigger FBG than that in AA genotypes (P＜0.05). Finally, we observedthe effect of this variation on rosiglitazone response. Our results show that patients withAA genotype of leptin (G-2548A) had higher differential values (after and beforeadministration) in Fins and Pins than that in GG+GA genotype after 12 weeks ofrosiglitazone treatment (P＜0.05). The allelic frequency of-308A (TNF-α) in patients withtype 2 diabetes and health control were 5.1% and 5.3%, respectively. No significantdifference was observed between two groups (P＞0.05). The variation of -308A allelewas not associated with BMI,leptin, FBG,FINS,HOMA-IR and HbAlc in patients withtype 2 diabetes (P＞0.05); However, patients with GA+ AA genotype of TNF-α(G-308A) had lower value of FINS than that in GG genotype after 12 weeks of rosiglitazonetreatment (P＜0.05).Conclusions: We found that the genetic polymorphisms of leptin G-2548A andTNF-αG-308A appear not to be influence on the development of type 2 diabetes. Thesedate suggest that genetic polymorphism of leptin and TNF-αgenes might affect thetherapeutic efficacy of rosiglitazone in patients with type 2 diabetes.
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