Association of GCLM -588C/T and GCLC -129T/C Promoter Polymorphisms of Genes Coding the Subunits of Glutamate Cysteine Ligase with Ischemic Heart Disease Development in Kazakhstan Population.

Liliya Skvortsova,Alma Mansharipova,Leyla Djansugurova,Elmira Khussainova,Henry Jay Forman,Anastasia Perfelyeva

doi:10.1155/2017/4209257

Abstract

Background Glutamate cysteine ligase (GCL) is a rate-limiting enzyme in synthesis of glutathione. Evidence suggests that genetic variations in the promoter region of genes coding a catalytic subunit (GCLC -129T/C) and a modifier subunit (GCLM -588C/T) of GCL have a functional impact on their transcriptional activity and were associated with various disorders. Hence, we hypothesize whether these two polymorphic variants of GCLM and GCLC genes are associated with the risk of ischemic heart disease (IHD) development in the population of Kazakhstan. Methods We evaluated 360 patients with IHD and 341 control subjects. Allele frequencies of studied promoters' polymorphisms were detected by PCR-RFLP analysis. Multiple logistic regression analysis was applied to assess the risk for different genotypes obtained. Results The presence of -588T allele in GCLM and -129T allele in GCLC gene genotypes was associated with an increased risk of IHD (GCLM -588T: OR = 3.92, p = 0.003; GCLC -129T: OR = 3.22, p = 0.03) for general ethnically mixed group. Analysis of each ethnical groups separately showed the higher risk tendency for Kazakhs as for GCLM -588T (OR = 4.79; p = 0.03) and as for GCLC -129T (OR = 4.79, p = 0.03). For Russians, statistically differences for two polymorphisms were not observed. Conclusion The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population.

Highlights

Nowadays, ischemic heart disease (IHD) is a major health problem due to the high prevalence of morbidity and mortality both in economically developed countries and in Kazakhstan
A total of 360 IHD patients with angina pectoris and 341healthy subjects were selected for the “case-control” study
We found that GCLM -588TT genotype was associated statistically with higher risk of IHD in females (OR = 3 97, 95%CI = 0 85–18 54, χ2 = 10 812, p = 0 004) and in individuals older than 45 years (OR = 2 91, 95%CI = 0 80–10 53, χ2 = 6 097, p = 0 04)

Summary

Introduction

Ischemic heart disease (IHD) is a major health problem due to the high prevalence of morbidity and mortality both in economically developed countries and in Kazakhstan. Despite the fact that the opening of the classic risk factors has reduced mortality from IHD in many developed and developing countries, the incidence of IHD continues to grow steadily every year. Perhaps, this is due to that IHD is a multifactorial disease and the body’s response to these environmental risk factors is under individual genetic control. We hypothesize whether these two polymorphic variants of GCLM and GCLC genes are associated with the risk of ischemic heart disease (IHD) development in the population of Kazakhstan. The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population

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