Association between MIF gene promoter rs755622 and susceptibility to coronary artery disease and inflammatory cytokines in the Chinese Han population

Jun-Yi Luo,Xiao-Mei Li,Guo-Li Du,Yan-Hong Li,Ting Tian,Yi-Ning Yang,Fen Liu,Bin-Bin Fang,Xiao-Ming Gao

doi:10.1038/s41598-021-87580-6

Abstract

Macrophage migration inhibitory factor (MIF) is an essential mediator of atherosclerotic plaque progression and instability leading to intracoronary thrombosis, therefore contributing to coronary artery disease (CAD). In this study, we investigated the relationship between MIF gene polymorphism and CAD in Chinese Han population. Three single nucleotide polymorphisms (SNP, rs755622, rs1007888 and rs2096525) of MIF gene were genotyped by TaqMan genotyping assay in 1120 control participants and 1176 CAD patients. Coronary angiography was performed in all CAD patients and Gensini score was used to assess the severity of coronary artery lesions. The plasma levels of MIF and other inflammatory mediators were measured by ELISA. The CAD patients had a higher frequency of CC genotype and C allele of rs755622 compared with that in control subjects (CC genotype: 6.5% vs. 3.9%, P = 0.008, C allele: 24.0% vs. 20.6%, P = 0.005). The rs755622 CC genotype was associated with an increased risk of CAD (OR: 1.804, 95%CI: 1.221–2.664, P = 0.003). CAD patients with a variation of rs755622 CC genotype had significantly higher Gensini score compared with patients with GG or CG genotype (all P < 0.05). In addition, the circulating MIF level was highest in CAD patients carrying rs755622 CC genotype (40.7 ± 4.2 ng/mL) and then followed by GC (37.9 ± 3.4 ng/mL) or GG genotype (36.9 ± 3.7 ng/mL, all P < 0.01). Our study showed an essential relationship between the MIF gene rs755622 variation and CAD in Chinese Han population. Individuals who carrying MIF gene rs755622 CC genotype were more susceptible to CAD and had more severe coronary artery lesion. This variation also had a potential influence in circulating MIF levels.

Highlights

Coronary artery disease (CAD), the leading cause of mortality and disability, increases the burden of healthcare costs worldwide[1]
We found that the coronary artery disease (CAD) patients had higher levels of low density lipoprotein-cholesterol (LDL-C), TG, total cholesterol (TC) and glucose and lower high density lipoprotein- cholesterol (HDL-C) level versus control participants
CAD patients were older and had a higher prevalence of hypertension and diabetes than control group, while gender ratio, smoking, Body mass index (BMI) were comparable between the two groups

Summary

Introduction

Coronary artery disease (CAD), the leading cause of mortality and disability, increases the burden of healthcare costs worldwide[1]. Different from the roles in acute myocardial injury, chronically elevated MIF exerts pro-inflammatory actions in ischemic m yocardium[24] and atherosclerosis, for example, in the development of atherosclerosis, elevated MIF promotes the recruitment of mononuclear cells and the conversion of macrophages into foam c ells[18]. MIF is known as a multifunctional inflammatory cytokine, playing a significant role in the progression of atherosclerosis, it may be a critical contributor of CAD and acute MIF release and chronically elevated MIF play distinct roles in ischemic heart disease. Genetic epidemiology studies have demonstrated that MIF gene variation was associated with various inflammatory diseases including rheumatic heart disease[25], metabolic syndrome[26], rheumatoid arthritis[27], ulcerative colitis28, psoriasis[29], and systemic sclerosis[30]. We investigated potential functional consequence of MIF gene variant by measuring levels of inflammatory biomarkers

Methods

Results

Conclusion