Clinical Practice in Pediatrics

Influence of polymorphisms of some genes on parameters of nerve conduction in children with diabetes mellitus type 1

The objective. To conduct comprehensive search for genetic risk factors of diabetic distal polyneuropathy (DDP) and to study relationship between single-nucleotide polymorphisms of 10 genes (11 polymorphisms) and parameters of conduction of peripheral nerve stimulation in the lower extremities in children with diabetes mellitus (DM) type 1.
Patients and methods. The examination included 45 children (18 girls and 27 boys with DM type 1 aged 7 to 17 years; mean age 14.13 ± 2.52 years. Children were treated in the endocrinological department of Kiev’s Children’s Clinical Hospital No 6. Duration of disease varied from 3 to 16 years, averaging 6.23 ± 3.54 years. The state of nerve conduction was examined by the method of electroneuromyography; dorsal latency С; (ms) and nerve conduction velocity (m/s) in motor fibres of the fibular and tibial nerves on both sides were determined. Also factors significantly influencing conduction of stimulation in nerve fibres were taken into account (level of carbohydrate metabolism compensation, duration of disease). DNA isolated from buccal epithelium was used for genotyping. Polymerase chain reaction was performed both in real time mode and with subsequent electrophoresis of obtained amplificates and analysis of the length of restriction fragments. We also studied gene polymorphisms encoding: endothelial NO synthase (eNOS); elastine (ELN); B-type natriuretic peptide (NPPB); angiotensin converting enzyme (АСЕ); one of inducible proteasome units (LMP2); angiotensinogen (AGT); angiotensin II type 1 receptors (ATR1); metalloproteinases -9 and -2 (MMP9, MMP2); proteasome subunit alpha type-6 (PSMA6).
Results. In examining Т-786→С eNOS gene polymorphism we have found that 21 (46.6%) children with heterozygous genotype had the lowest values of dorsal latency (4.30 ± 0.17 ms) and the highest nerve conduction velocity (54.89 ± 1.19 m/s). In examining A1166→C ATR1 gene polymorphism we have found that 6 (13%) children homozygous for C allele had the lowers dorsal latency (4.08 ± 0.48 ms), and the highest mean nerve conduction velocity (51.40 ± 2.79 m/s). Absence of significant differences in the average HbA1c level and average duration of disease between groups of patients with different genotypes is indicative of a relationship between these polymorphisms and parameters of nerve conduction.
Conclusion. As has been found, Т/Т genotype in Т-786→С eNOS gene polymorphism is a genetic risk factor for DDP and heterozygosity for this polymorphism has a protective character. C allele and С/С genotype in A1166→C ATR1 gene polymorphism are protective genetic factors of this complication.
Key words: diabetic polyneuropathy, single nucleotide polymorphism, type 1 diabetes mellitus.
Publisher's imprint: V.G.Maydannik, V.E.Dosenko, N.B.Pranik. Influence of polymorphisms of some genes on parameters of nerve conduction in children with diabetes mellitus type 1. Clinical Practice in Pediatrics. 2015;10(2):7-13.

Received: 10.01.2015