Skvortsova Liliya, Perfelyeva Anastasia, Khussainova Elmira, Mansharipova Alma, Forman Henry Jay, Djansugurova Leyla
Institute of General Genetics and Cytology, Al-Farabi St. 93, Almaty, Kazakhstan.
Russian Medical University, Torekulovst 71, Almaty, Kazakhstan.
Dis Markers. 2017;2017:4209257. doi: 10.1155/2017/4209257. Epub 2017 Jul 5.
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.
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.
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, = 0.003; GCLC -129T: OR = 3.22, = 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; = 0.03) and as for GCLC -129T (OR = 4.79, = 0.03). For Russians, statistically differences for two polymorphisms were not observed.
The two promoter polymorphisms of GCLM (-588C/T) and GCLC (-128T/C) are associated with an increased risk of IHD in Kazakhstan population.
谷氨酸半胱氨酸连接酶（GCL）是谷胱甘肽合成中的限速酶。有证据表明，编码GCL催化亚基（GCLC -129T/C）和调节亚基（GCLM -588C/T）的基因启动子区域的遗传变异对其转录活性有功能影响，并与多种疾病相关。因此，我们推测GCLM和GCLC基因的这两种多态性变体是否与哈萨克斯坦人群缺血性心脏病（IHD）的发生风险相关。
我们评估了360例IHD患者和341例对照受试者。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析检测所研究启动子多态性的等位基因频率。应用多因素逻辑回归分析评估所获得的不同基因型的风险。
对于一般种族混合组，GCLM基因-588T等位基因和GCLC基因-129T等位基因的存在与IHD风险增加相关（GCLM -588T：比值比[OR]=3.92，P=0.003；GCLC -129T：OR=3.22，P=0.03）。分别对每个种族组进行分析显示，哈萨克人在GCLM -588T（OR=4.79；P=0.03）和GCLC -129T（OR=4.79，P=0.03）方面有更高的风险倾向。对于俄罗斯人，未观察到两种多态性的统计学差异。
GCLM（-588C/T）和GCLC（-128T/C）的两种启动子多态性与哈萨克斯坦人群IHD风险增加相关。
