Homozygosity of the Z‐2 polymorphic variant in the aldose reductase gene promoter confers increased risk for neuropathy in children and adolescents with Type 1 diabetes

Background Diabetic neuropathy(DN) is the least recognized complication of diabetes mellitus and may start early in the course of disease. Aldose reductase(AKR1B1) gene promoter Z-2/Z-2 polymorphism increases the expression of AKR1B1enzyme and may contribute to DN. Subjects We evaluated 108 type 1 diabetes(T1D) children and adolescents (mean±SD age:13.5±3.46 years, disease duration:5.3±3.4 years) and 150 healthy controls (age:11.9±2.7 years). Methods In both groups, pupillary dilation(PD) in darkness, postural blood pressure test(PBPT) and vibration sensation thresholds(VST) in upper and lower limbs were estimated as indices of autonomic and peripheral neuropathy, respectively. Nerve conduction studies(NCS) were performed in patients as peripheral neuropathy index. The polymorphisms of AKR1B1gene were evaluated using microsatellite(AC)n sequence Z. Results PBPT, PD and VST impairments were more frequent in patient group compared with controls, while 38.6% of patients exhibited NCS abnormality. Gender, age, pubertal status, height, BMI, diabetes duration, HbA1c and anti-GAD titers were associated with neuropathy indices in patients. There was a strong correlation between PD and NCS in patients, while homozygous patients for Z-2 AKR1B1 gene polymorphism had higher prevalence of abnormal NCS (83.3% vs 34.6%), PD (62.5% vs 31,5%) and PBPT values compared with heterozygous or negative patients. Homozygous AKR1B1 status predicted PD, NCS and PBPT variance, while PD, VST, NCS and PBPT parameters accurately discriminated homozygous AKR1B1 patients. Conclusions Impaired indices of peripheral and autonomic DN were present in a significant proportion of young T1D patients. PD, VST, NCS and PBPT parameters were simultaneously associated with homozygous state of AKR1B1 Z-2 gene polymorphism, implicating polyol metabolism with both autonomic and peripheral neuropathies. This article is protected by copyright. All rights reserved.