Ministry of Health of the Republic of Uzbekistan
Title: Association of 1Î² IL1B (rs1143634) and Î± TNFA (rs1800629) Gene Polymorphisms in Peptic Ulcer Development in the Uzbekistan Republic
INTRODUCTION: Peptic ulcer disease (PUD) is a chronic recurrent disease characterized by the alternation of exacerba tion and remission periods and the formation of a defect (ulcer) in the stomach and (or) duodenum wall that penetrates into the submucosal layer. PUD represents one of the most frequent diseases of the gas trointestinal tract, with a frequency about 10% world wide. PUD might result in the loss of work capacity or even in lethality: mortality from this pathology varies in different countries, from 6 to 7.1 per 100000 for gas tric ulcer and from 0.2 to 9.7 for duodenal ulcer. The present study aimed to study the association of polymorphic variants of interleukin 1β IL1B (rs1143634) and tumor necrosis factor α TNFA (rs1800629) genes with PUD in Uzbekistan Republic (UzR).
MATERIALS AND METHODS: The material for the study included DNA samples obtained from individuals with PUD and healthy donors aged 16–80 years. The patient group was composed of 148 individuals ( diag nosed with duodenal ulcer and 67 with gastric ulcer and mixed PUD forms) of various ethnicity of Uzbekistan.
Genomic DNA was isolated from peripheral blood lymphocytes via the phenol chloroform extraction technique. Amplification of the studied polymor phisms was carried out via polymerase chain reaction of DNA synthesis on a GeneAmp PCR System 2720 (Applied Biosystems, United States).
RESULTS: An analysis of the allele and genotype frequencies of several polymorphic variants of interleukin 1β IL1B (rs1143634) and tumor necrosis factor α TNFA (rs1800629) genes was conducted in PUD patients and control individuals from the Uzbekistan Republic. The observed distribution of genotype frequencies was in accordance with that expected in accordance with the Hardy–Weinberg equilibrium.
Comparative analysis of the allele and genotype frequency distributions of rs1143634 for PUD patients and the control group demonstrated statistically significant differences in Uzbeks: the rs1143634*C allele was observed in 79.60% of patient chromosomes and in 84.20% of chromosomes from the control group, and the rs1143634*C/C genotype was detected in 69.10% in PUD individuals as compared to the relevant control group (60.50%). These variants represent markers of high risk of developing PUD (χ2 =1.50, p = 0.2; OR = 1.40; 95% CI 0.82–2.24 and χ2 = 1.0, p = 0.2; OR = 1.3; 95% CI 0.88–2.074, respectively). Moreover, markers of decreased risk of developing PUD were revealed for ethnic Uzbeks: the rare rs1143634*T allele was detected in 20.40% of patients, compared to 15.80% in the control group (χ2 < 3.80, p > 0.05;) and the heterozygous rs1143634*C/T genotype was observed in 38.30% of PUD patients and in 32.20% of healthy donors.
The distribution of allele and genotype frequencies of –308G>A (rs1800629) polymorphism located in the promoter region of the TNFA gene is shown the highest frequency was observed for the rs1800629*G allele (85.20% in PUD patients 92.10% in the control group) and for the G/G genotype (70.40% in patients, 84.20% in control group). How ever, homozygosis for the rare allele rs1800629*A/A genotype was observed in less than 3% of cases. Analysis of the allele and genotype frequency distributions demonstrated the absence of statistically significant differences between the studied PUD samples and control individuals.
DISCUSSION: Intergenic interaction was established and combinations of polymorphic variants of rs1800629 polymorphisms of gene TNFα rs1143634 of IL-1β gene were determined in the determination of the risk of duodenal ulcer and chronic gastritis. The heterozygous haplotype of these genes is a predisposing factor to the formation of duodenal ulcer and chronic gastritis..