Association of type 2 diabetes susceptibility loci with peripheral nerve function in a Chinese population with diabetes

Aims/introduction: Previous studies have suggested a possible relationship between type 2 diabetes mellitus susceptibility loci and diabetic complications. The present study aimed to investigate the associations between type 2 diabetes mellitus loci with peripheral nerve function in a Chinese population with type 2 diabetes mellitus.

Materials and methods: A total of 1,900 type 2 diabetes mellitus patients were recruited in the study. We selected ten single nucleotide polymorphisms (SNPs) from ten type 2 diabetes mellitus susceptibility genes previously confirmed in Chinese patients. Genotyping was carried out by using a MassARRAY Compact Analyzer. Peripheral nerve function was evaluated by nerve conduction studies in all participants. The composite Z-scores for nerve conduction parameters including conduction velocity (CV), amplitude and latency were calculated, respectively.

Results: Rs5219 of KCNJ11 (E23K, G→A) was identified to be associated with all the parameters obtained from nerve conduction studies (Z-score of CV: β = 0.113, P = 0.01; Z-score of amplitude: β = 0.133, P = 0.01; Z-score of latency: β = -0.116, P = 0.01) after adjustment for covariates including age, duration and glycated hemoglobin. Specifically, each copy of the A allele was related to better outcomes. CDKAL1 rs7756992 and TCF7L2 rs7903146 correlated with the composite Z-score of amplitude (P = 0.028 and P = 0.016, respectively), but not CV (P = 0.393 and P = 0.281, respectively) or latency (P = 0.286 and P = 0.273, respectively). There were no significant associations between the other seven SNPs and peripheral nerve function.

Conclusions: Rs5219 at KCNJ11 (E23K) was associated with peripheral nerve function in a Chinese population with type 2 diabetes mellitus, suggesting shared genetic factors for type 2 diabetes mellitus and diabetic polyneuropathy in this population.