Association of adiponectin gene polymorphisms with an elevated risk of diabetic peripheral neuropathy in type 2 diabetes patients

Objective In this study, we examined the association between two adiponectin (ADPN) gene polymorphisms, +45T/G and +276G/T, and susceptibility to diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients. Methods A total of 180 T2DM patients were enrolled in this study and assigned to two groups: DPN group (n=90) and non-DPN (NDPN) group (n=90). In addition, 90 healthy subjects were chosen as healthy normal control (NC). The plasma level of ADPN was quantified by ELISA method and polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) was used for genotype analysis of the two ADPN polymorphisms, +45T/G (rs2241766) and +276G/T (rs1501299), in all the study subjects. Statistical analysis of data was performed with SPSS version 20.0 software. Results Serum levels of ADPN were markedly reduced in the DPN group compared to NDPN and NC groups (all P<0.05). The frequencies of TT, TG and GG genotypes and the T and G alleles of T45G and G276T polymorphisms in DPN group were significantly different than the NDPN group (all P<0.05). Notably, T45G and G276T polymorphisms were associated with significantly reduced plasma levels of ADPN in DPN and NDPN groups, compared to the NC group (P<0.001). Significant difference in ADPN plasma levels were also observed between TT, TG and GG genotypes of T45G and G276T polymorphisms. Our results indicate that the T allele in +45T/G and +276G/T polymorphisms is correlated with an elevated risk of DPN in T2DM patients. Haplotype analysis showed that GG and GT haplotypes showed a negative relationship with DPN, while TG haplotype positively correlated with risk of DPN in T2DM patients (all P<0.05). Conclusion Our results show that T45G and G276T polymorphisms of ADPN are associated with a significantly elevated risk of DPN in T2DM patients, likely by down-regulating ADPN serum level.