ACE gene polymorphism and features of kidney disorders in patients with type 2 diabetes mellitus

Abstract

Objective — to determine the prevalence of the Alu Ins/Del polymorphism of the angiotensin‑converting enzyme (ACE) gene in patients with type 2 diabetes mellitus (DM 2) with nephropathy and to identify possible associative relationship between the course of the disease and the genetic profile of the examined subjects.
 Materials and methods. Examinations involved 73 patients with diabetic nephropathy (DN), treated in the hospital of L. T. Mala Therapy National Institute. The control group consisted of 19 healthy individuals. After the initial examination and depending on the polymorphic variant of the ACE gene, patients were divided into three groups: group I — carriers of D/D polymorphism of the ACE gene (n = 23); group II — patients with I/D polymorphism of the ACE gene (n = 32); Group III — patients with I/I polymorphism of the ACE gene (n = 18). DNA amplification and genotyping were carried out by real‑time polymerase chain reaction (PCR) using the SNP‑Express‑Shot reagent kit (Litech, RF) and the CFX96 touch real‑time PCR product detection system (BioRad).
 Results. The distribution of the genotypes of the Alu I/D polymorphism of the ACE gene corresponded to the Hardy‑Weinberg equilibrium in all studied groups and did not differ significantly from European populations. Comparison of patients with DN, carriers of different Ins/Del polymorphic variants of the ACE gene, did not show significant differences in the stages of chronic kidney disease, creatinine level, and glomerular filtration rate (GFR). Patients with type 2 DM, homozygous for the I/I allele of the ACE gene, had significantly lower levels of urinary albumin (16.80 [12.61 — 34.20] mk/ mL), compared with I/D heterozygotes (26.07 [20.91 — 44.27] mkg/mL), p < 0.05, which demonstrates the negative effects of D allele on the kidney damage progression in this category of patients, even under the same GFR.
 Conclusions. Patients with DN who are homozygous for the ACE gene allele I, have significantly lower albumin levels than I/D heterozygotes, demonstrating an association between the D allele and the progression of renal disease in type 2 DM. Determining the ACE gene polymorphism in patients with type 2 DM allows to identify risk groups for the DN development and will help to make individualized adjustments to the scheme of pharmacological therapy.