Genetic variants of ALR (-106C → T /-12C → G) and serum PKC-δ are associated with peripheral neuropathy in Egyptian diabetic patients with impaired handwriting.

PURPOSE

Diabetic peripheral neuropathy can injure the hand median nerve and cause extensive nerve damage. PKC and ALR are associated with progression of diabetic complications. We hypothesized a genetic association between the ALR polymorphisms (-106C → T/-12C → G) and elevated serum PKC-δ levels in diabetic neuropathy and its adverse effects on handwriting in Egyptian population.

METHODS

One hundred DPN were compared with 100 DP and 100 healthy volunteers. ALR -106C → T/-12C → G variants were studied using the PCR-RFLP method. A routine set of standard laboratory markers was determined. Serum PKC-δ concentration was determined by ELISA. Logistic regression analysis and areas under the receiver characteristic curves (AUCs) were evaluated to investigate the predictors of diabetic neuropathy. Arabic handwriting was analyzed based on the recognition of functional features, word shape, and ascending/descending parts of letters.

RESULTS

Individuals carrying ALR-106C → C and -12G → G had a significantly higher risk of developing diabetic neuropathy than individuals with -106C → T and -12C → G genotypes ( = 0.01,  = 0.02). Carriers of the (-106C → T) CC and (-12C → G) GG genotypes had significantly increased serum levels of PKC-δ, FBG, TC, and LDL-c. PKC- δ serum levels were significantly correlated with glycemic and lipid indicators ( < 0.001). PKC-δ is a significant predictor of diabetes with or without neuropathy at a cutoff value of 16.6, sensitivity was 89%, and specificity 100%. All DPN showed complete deterioration of handwriting after the onset of diabetic neuropathy.

CONCLUSION

The genetic variants ALR-106C → C / -12G → G and PKC-δ in serum may help in the detection and treatment of diabetic neuropathy in Egyptian population before writing performance is affected.