Interactive effects of interferon-gamma functional single nucleotid polymorphism (+874 T/A) with cardiovascular risk factors in coronary heart disease and early myocardial infarction risk

Abstract

Atherosclerosis is an inflammatory disease characterized by extensive lipid accumulation in the artery wall. Throughout the atherosclerotic process, interferon-gamma (IFN-gamma), which is an important pro-inflammatory cytokine, plays a central role in atherosclerotic plaque instability and the occurrence of myocardial infarction (MI). In this study, we aimed to investigate the relationship between IFN-gamma +874 T/A (rs2430561) polymorphism and coronary heart disease (CHD) as well as its effects on MI and CHD. Three hundred and ninety patients with CHD (229 with MI, 161 without MI) and 233 healthy controls were screened by the amplification refractory mutation system (ARMS) PCR method for IFN-gamma +874 T/A polymorphism. For MI risk, early adult age was important risk factors and the risk was increased with IFN-gamma +874 T/A polymorphism. IFN-gamma T allele was significantly increased in the CHD patients with age <= 45 (p = 0.048) and patients with history of MI (p = 0.007). As IFN-gamma is an inflammatory cytokine with an emerging role in the atherosclerotic process, it was suggested that inhibition of IFN-gamma activity could be a therapeutic strategy to stabilize human atherosclerotic plaque. Our findings support the association between MI risk and IFN-gamma +874 T/A polymorphism in the Turkish population, particularly by increasing the level of IFN-gamma in young patients, thereby causing rupture of vulnerable plaques in atherosclerotic lesions. Identification of the IFN-gamma +874 T/A gene variants as risk factors for early CHD and MI development may be a practical biomarker to guide the MI risk process and determine the ideal therapeutic approach.