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Polymorphism of genes of the renin-angiotensin system ACE, ATIR, and AT2R in patients with pulmonary tuberculosis
Authors:O B Ogarkov  V V Sinkov  T V Medvedeva  M Yu Gutnikova  O M Nekipelov  L Yu Raevskaya  N Yu Kuptsevich  K Yu Kostyunin  R G Skvortsova
Institution:(1) Irkutsk Regional Diagnostic Center, Irkutsk, Russia;(2) Irkutsk Regional Anti-Tuberculosis Hospital, Irkutsk, Russia;(3) Irkutsk City Anti-Tuberculosis Hospital, Irkutsk, Russia
Abstract:The investigation was aimed at testing the hypothesis on the possible role of some genes of the renin-angiotensin system in the formation of innate immunity to tuberculosis. It is known that insertion-deletion (I/D) polymorphism of the gene encoding the angiotensin-converting enzyme (ACE) influences the concentration of angiotensin II in the human organism and, indirectly, many stages of metabolism. On one hand, homozygotes of deletion in the ACE gene (DD genotype) are characterized with obesity, arterial hypertension, hypocholesterolemia, and some other pathological conditions. On the other hand, it was demonstrated that hypercholesterolemia is common pathology for patients with pulmonary tuberculosis (C. Perez-Guzman et al., 2005). The investigation of insertion-deletion polymorphism of the ACE gene (genotypes DD, ID and II), single nucleotide polymorphism at position 1166 of the AT1R gene (1166 A/C), and analogous transversion at position 3123 of the AT2R gene (3123 A/C) was carried out. A group of 200 patients with tuberculosis 202 patients with essential hypertension and 208 healthy individuals were analyzed. A group of patients with essential hypertension was used as a contrast sample. According to hypothesis, a statistically significant excess number was found of carriers of genotype DD (ACE) in patients with hypertension as compared to the group of patients with tuberculosis (χ2 = 9.64; ρ = 0.0019; OR = 2.0; CI 1.2, 3.3). The tendency toward an increase in the amount of DD genotypes was observed in comparisons of patients with tuberculosis and healthy patients with hypertension, although these differences did not reach significant values in the given study. A comparison of genotypes and allelotypes in group of patients with tuberculosis and both control groups (healthy and patients with hypertension) was performed. A significant difference was observed in the group of male patients with tuberculosis, though not female, when comparing with control groups. It had been demonstrated that the most important contribution is made by the ACE and AT2R genes. Genotype ID + 3123C (genes ACE and AT2R) was found significantly more often in male patients with tuberculosis than in the control group of healthy individuals (χ2 = 9.70; ρ = 0.002; OR = 2.3; CI 1.2s-4.3). The obtained results were discussed.
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