Interleukin-27 polymorphisms are associated with premature coronary artery disease and metabolic parameters in the Mexican population: the genetics of atherosclerotic disease (GEA) Mexican study

Abstract

Several studies suggest an important role of Interleukin-27 in the development of atherosclerosis. The aim of this study was to establish whether the IL-27p28 gene polymorphisms are associated with premature coronary artery disease and/or other cardiovascular risk factors. Four IL-27p28 gene polymorphisms were selected and genotyped in 1162 premature coronary artery disease cases and 1107 controls. rs26528 T and rs40837 A alleles were significantly associated with a lower risk of premature coronary artery disease under different inheritance models (Pdominant = 0.046; Pover-dominant = 0.002; Pco-dominant1 = 0.007 for rs26528T; Pover-dominant = 0.008 and Pco-dominant1 = 0.031 for rs40837). The rs40837 A allele was also associated with a lower risk of insulin resistance, in cases (Pover-dominant = 0.037) and controls (Padditive = 0.008; Pdominant = 0.047; Precessive = 0.014; Pco-dominant2 = 0.006), while the rs26528 T allele was associated with a lower risk of insulin resistance only in the control group (Precessive = 0.016; Pco-dominant2 = 0.021). Interleukin-27 plasma levels were measured in 450 controls and 450 cases, and were significantly higher in cases compared to controls (P = 0.004). However, Interleukin-27 plasma levels were not associated with IL-27p28 polymorphisms. Luciferase assays showed that co-transfection of the rs40837 A allele and miR-379-5p significantly decreased luciferase gene expression. Our study shows for the first time, that IL-27p28 gene polymorphisms are associated with premature coronary artery disease and with some metabolic parameters. The rs40837 A allele in presence of miR-379-5p significantly decreased luciferase gene expression.

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

“…In a large number of CAD cases belonging to the GeneID Chinese Han population, four IL-27p28 tag polymorphisms (rs181206, rs17855750, rs37833, and rs153109) were detected and after adjusting for confounding variables, the polymorphisms were not associated with CAD, age at disease onset or severity 137 . These results concur well with the findings of the Genetics of Atherosclerotic Disease (GEA) Study in a Mexican population, in which the rs181206 and rs17855750 IL-27p28 gene variants were not significantly associated with premature CAD 98 . However, Posadas-Sánchez et al reported a significant association (after adjusting for age, gender, body mass index, smoking habit, total abdominal fat, homeostatic model assessment-insulin resistance, aspartate aminotransferase, adiponectin, and uric acid) of both the rs26528 T and rs40837 A alleles with a decreased risk of developing premature CAD 98 .…”

“…These results concur well with the findings of the Genetics of Atherosclerotic Disease (GEA) Study in a Mexican population, in which the rs181206 and rs17855750 IL-27p28 gene variants were not significantly associated with premature CAD 98 . However, Posadas-Sánchez et al reported a significant association (after adjusting for age, gender, body mass index, smoking habit, total abdominal fat, homeostatic model assessment-insulin resistance, aspartate aminotransferase, adiponectin, and uric acid) of both the rs26528 T and rs40837 A alleles with a decreased risk of developing premature CAD 98 . In addition, luciferase assays showed that cotransfection of the rs40837 A allele and miR-379-5p significantly decreased luciferase gene expression.…”

“…In contrast, in a clinical study of 136 CAD patients and 29 controls, Jin et al found that IL-27 plasma concentration was higher and correlated with the severity of the coronary atherosclerotic lesion in CAD patients 97 . Similarly, significantly higher IL-27 plasma concentrations were observed in Mexican premature CAD patients compared to controls 98 . Moreover, dendritic cells incubated with oxidized low-density lipoprotein produced IL-27, suggesting that these modified lipoproteins could play an important role in dendritic cell activation and IL-27 production 97 .…”

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges

“…An IL-23R polymorphism was observed to be related to coronary artery disease, and the IL-23R rs6682925T/C polymorphism may independently relate to the presence of coronary artery disease (Zhang et al, 2014a). IL-27 gene polymorphism had no effect on the presence of subclinical atherosclerosis, while closely related to atherosclerosis and coronary artery disease, rs26528 T and rs40837 A alleles significantly reduced the risk of coronary artery disease (Posadas-Sánchez et al, 2017;Vargas-Alarcón et al, 2019). No research about gene polymorphisms of IL-12 and IL-35 and the presence of coronary artery disease was reported yet.…”

IL-27: a double agent in the IL-6 family

“…Equally, genetic variants associated with IL6st (gp130; rs10940495) and IL6R (rs2228145) are common to patients with cardiovascular disease and rheumatoid arthritis . Several polymorphisms linked with IL27 (encoding IL‐27p28; rs153109, rs181206, rs17855750) also display risk susceptibilities with asthma, certain cancers, metabolic disorders and some viral infections . For example, rs153109 is linked to more severe forms of rheumatoid arthritis .…”