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

Abstract EN

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.