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.