Hoseini Fatemeh, Mahmazi Sanaz, Mahmoodi Khalil, Jafari Gholam Ali, Soltanpour Mohammad Soleiman
Department of Genetic, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran.
Department of Cardiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
Oman Med J. 2018 Mar;33(2):118-125. doi: 10.5001/omj.2018.23.
Interleukin-18 (IL-18) is a proinflammatory and proatherogenic cytokine, and its genetic variations may contribute to the development of coronary artery disease (CAD). We sought to investigate the role of -137G/C polymorphism and gene expression levels of IL-18 in patients with CAD.
The study population included 100 patients with angiographically proven CAD and 100 matched controls. Total RNA and DNA were extracted from leukocytes using appropriate kits. The genotype of -137G/C polymorphism and gene expression level of IL-18 was determined using allele-specific polymerase chain reaction (PCR) and real-time (RT)-PCR assay, respectively.
The genotypic and allelic distribution of IL-18 -137G/C polymorphism was not significantly different between the two groups ( > 0.050). Moreover, the -137G/C polymorphism did not increase the risk of CAD in dominant and recessive genetic models ( > 0.050). However, subgroup analysis of CAD patients revealed that the IL-18 -137G/C polymorphism was significantly associated with increased risk of CAD in hypertensive patients (odds ratio (OR) = 7.51; 95% confidence interval (CI): 1.24-25.17; 0.019) and smokers (OR = 4.90; 95% CI: 1.21-19.70; 0.031) but not in the diabetic subpopulation ( 0.261). The genotype distribution of IL-18 -137G/C genetic polymorphism was significantly different among patients with one, two, and three stenotic vessels ( < 0.050). The gene expression level of IL-18 was significantly higher in the CAD group than the control group ( < 0.001). Moreover, the carriers of CC genotype had significantly lower gene expression levels of IL-18 than carriers of GG genotype ( < 0.050).
The -137G/C polymorphism of IL-18 may be associated with the CAD risk in hypertensive and smoker subgroup of CAD patients. The -137G/C polymorphism seems to play an important role in determining the severity of CAD. Increased IL-18 gene expression level is a significant risk factor for the development of CAD. The CC genotype of -137G/C polymorphism is associated with lower IL-18 gene expression levels.
白细胞介素-18（IL-18）是一种促炎和促动脉粥样硬化细胞因子，其基因变异可能与冠状动脉疾病（CAD）的发生发展有关。我们旨在研究IL-18基因-137G/C多态性及其基因表达水平在CAD患者中的作用。
研究人群包括100例经血管造影证实的CAD患者和100例匹配的对照组。使用合适的试剂盒从白细胞中提取总RNA和DNA。分别采用等位基因特异性聚合酶链反应（PCR）和实时（RT）-PCR测定法确定IL-18基因-137G/C多态性的基因型和基因表达水平。
两组间IL-18基因-137G/C多态性的基因型和等位基因分布无显著差异（P>0.050）。此外，在显性和隐性遗传模型中，-137G/C多态性并未增加CAD的发病风险（P>0.050）。然而，对CAD患者的亚组分析显示，IL-18基因-137G/C多态性与高血压患者（比值比（OR）=7.51；95%置信区间（CI）：1.24-25.17；P=0.019）和吸烟者（OR=4.90；95%CI：1.21-19.70；P=0.031）患CAD的风险增加显著相关，但在糖尿病亚组中无相关性（P=0.261）。IL-18基因-137G/C多态性的基因型分布在单支、双支和三支血管狭窄的患者中存在显著差异（P<0.050）。CAD组中IL-18的基因表达水平显著高于对照组（P<0.001）。此外，CC基因型携带者的IL-18基因表达水平显著低于GG基因型携带者（P<0.050）。
IL-18基因-137G/C多态性可能与CAD患者中高血压和吸烟亚组的CAD风险相关。-137G/C多态性似乎在决定CAD的严重程度中起重要作用。IL-18基因表达水平升高是CAD发生发展的一个重要危险因素。-137G/C多态性的CC基因型与较低的IL-18基因表达水平相关。
