Raet1e Polymorphisms Are Associated with Increased Risk of Developing Premature Coronary Artery Disease and with Some Cardiometabolic Parameters: The GEA Mexican Study

Abstract

In an animal model, new evidence has been reported supporting the role of raet1e as an atherosclerosis-associated gene. Our objective was to establish if raet1e polymorphisms are associated with the risk of developing premature coronary artery disease (CAD) or with the presence of cardiometabolic parameters. After an informatic analysis, five polymorphisms were chosen and determined in 1158 patients with premature CAD and 1104 controls using 5′ exonuclease TaqMan genotyping assays. Standardized questionnaires were applied to all participants to obtain family medical history, demographic information, history of nutritional habits, physical activity, alcohol consumption, and pharmacological treatment. The functional effect of the rs7756850 polymorphism was analyzed by luciferase assays. Under different models, adjusted by age, gender, body mass index, current smoking, and type 2 diabetes mellitus, the rs6925151 (OR = 1.250, pheterozygote = 0.026; OR = 1.268, pcodominant1 = 0.034), rs9371533 (OR = 1.255, pheterozygote = 0.024), rs7756850 (OR = 1.274, pheterozygote = 0.016; OR = 1.294, pcodominant1 = 0.031), and rs9383921 (OR = 1.232, pheterozygote = 0.037) polymorphisms were associated with increased risk of premature CAD. When compared to the rs7756850 G allele, the C allele showed a decreased luciferase activity. In premature CAD patients, associations with low levels of adiponectin, with a high presence of hypertension, and with high levels of gamma-glutamyltransferase and total cholesterol were observed. In healthy controls, associations with a decrease in LDL pattern B, aspartate aminotransaminase, and hypo-α-lipoproteinemia were detected. An association of the raet1e polymorphisms with an increased risk of developing premature CAD and with cardiometabolic parameters has been shown for the first time. In addition, the functional effect of the rs7756850 polymorphism was defined.

ALOX5,LPA,MMP9andTPOgene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

“…The identification of early-onset CVDs susceptibility polymorphisms in the Mexican population is crucial because the morbidity and mortality rates have risen substantially in the last years [30,31]. Herein, the collective contribution of nine genes (ALOX5, IL6, LPA, MMP9, vWA, eNOS, HMOX1, NOX4 and TPO) was investigated in middle-aged Mexican subjects with and without clinical manifestations of atherothrombosis.…”

Characterisation of RAET1E/ULBP4 exon 4 and 3′ untranslated region genetic architecture reveals further diversity and allelic polymorphism

“…33,39 We previously found that five of the nine polymorphic positions within the 5 0 UTR promoter region of RAET1E alleles had potential to disrupt putative TF binding sites, 22 altering ligand expression level and affecting responses by NK cells or CD8+ T cells. Furthermore, a study published in 2018 40 found, using a luciferase assay, that 'C' allele at position À559 within the 5 0 UTR promoter region of ULBP4/RAET1E significantly reduced promoter activity by abrogating binding of T A B L E 5 Polymorphisms within the 5 0 UTR promoter, exons 1-3, exon 4 and 3 0 UTR regions of RAET1E. TF p53, contributing to increased risk of chronic artery disease.…”

Effect of ABCA1 promoter methylation on premature coronary artery disease and its relationship with inflammation

“…The expression of ABCA1 mRNA need to be further investigated. Third, as the definition of pCAD is not uniformly established, and consider the actual situation of our centre and various literature studies [4][5][6][7], we used the common age cut-off value (before age 55 in men and 65 in women) in China, especially for women, due to the large age range, our findings may be more applicable to the relatively young patients with CAD.…”

“…Because pCAD has a long course and poor prognosis, its prevention and treatment is an urgent medical problem that needs to be addressed. However, the definition of pCAD was not uniformly established, the age cut-off can vary from 45 to 65 years among studies due to the variation in risk factors affecting different populations and ethnicities [3][4][5][6]. Chinese Studies on pCAD commonly used the definition of onset age < 55 years for males and < 65 years for females [7].…”