Evaluation of the Role of -137G/C Single Nucleotide Polymorphism (rs187238) and Gene Expression Levels of the IL-18 in Patients with Coronary Artery Disease

Fatemeh Hoseini; Sanaz Mahmazi; Khalil Mahmoodi; Gholam Ali Jafari; Mohammad Soleiman Soltanpour

doi:10.5001/omj.2018.23

Evaluation of the Role of -137G/C Single Nucleotide Polymorphism (rs187238) and Gene Expression Levels of the IL-18 in Patients with Coronary Artery Disease

Oman Med J. 2018 Mar;33(2):118-125. doi: 10.5001/omj.2018.23.

Authors

Fatemeh Hoseini¹, Sanaz Mahmazi¹, Khalil Mahmoodi², Gholam Ali Jafari³, Mohammad Soleiman Soltanpour⁴

Affiliations

¹ Department of Genetic, Faculty of Basic Sciences, Islamic Azad University, Zanjan Branch, Zanjan, Iran.
² Department of Cardiology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.
³ Department of Microbiology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
⁴ Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Abstract

Objectives: 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.

Methods: 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.

Results: The genotypic and allelic distribution of IL-18 -137G/C polymorphism was not significantly different between the two groups (p > 0.050). Moreover, the -137G/C polymorphism did not increase the risk of CAD in dominant and recessive genetic models (p > 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; p = 0.019) and smokers (OR = 4.90; 95% CI: 1.21-19.70; p = 0.031) but not in the diabetic subpopulation (p = 0.261). The genotype distribution of IL-18 -137G/C genetic polymorphism was significantly different among patients with one, two, and three stenotic vessels (p < 0.050). The gene expression level of IL-18 was significantly higher in the CAD group than the control group (p < 0.001). Moreover, the carriers of CC genotype had significantly lower gene expression levels of IL-18 than carriers of GG genotype (p < 0.050).

Conclusions: 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.

Keywords: Coronary Artery Disease; Gene Expression; Interleukin-18; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length.