Angeles-Martínez Javier, Posadas-Sánchez Rosalinda, Llorente Luis, Alvarez-León Edith, Ramírez-Bello Julian, Villarreal-Molina Teresa, Lima Guadalupe, Cardoso-Saldaña Guillermo, Rodríguez-Pérez José Manuel, Pérez-Hernández Nonanzit, Fragoso José Manuel, Posadas-Romero Carlos, Vargas-Alarcón Gilberto
Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, México.
PLoS One. 2017 Jan 3;12(1):e0168828. doi: 10.1371/journal.pone.0168828. eCollection 2017.
The effect of interleukin 33 (IL-33) in the inflammatory process generates significant interest in the potential significance of IL-33 as a biomarker for coronary artery disease (CAD). Here, our objective was to analyze whether IL-33 gene polymorphisms are associated with premature CAD in a case-control association study.
Four IL-33 polymorphisms (rs7848215, rs16924144, rs16924159 and rs7044343) were genotyped by 5' exonuclease TaqMan assays in 1095 patients with premature CAD and 1118 controls.
The rs7044343 T allele was significantly associated with a diminished risk of premature CAD (OR = 0.81, 95% CI: 0.69-0.97, Pdom = 0.020; OR = 0.85, 95% CI: 0.75-0.96, Padd = 0.019) and central obesity (OR = 0.74, 95% CI: 0.58-0.93, Pdom = 0.0007), respectively. When patients were divided into groups with and without type 2 diabetes mellitus (T2DM), the rs7044343 T allele was associated with a reduced risk of premature CAD in patients without (OR = 0.85, 95% CI: 0.73-0.99, Padd = 0.038) and with T2DM (OR = 0.61, 95% CI: 0.38-0.97, Pdom = 0.039; OR = 0.69, 95% CI: 0.49-0.97, Padd = 0.035). In order to establish the functional effect of the rs7044343 polymorphism, the production of IL-33 was determined in monocytes of selected individuals. Monocytes from individuals with rs7044343 CC genotype produced higher levels of IL-33 than monocytes from individuals with other genotypes.
The results suggest that the IL-33 rs7044343 T allele could be a susceptibility marker for premature CAD and central obesity. The rs7044343 polymorphism could be involved in regulating the production of IL-33.
白细胞介素33（IL-33）在炎症过程中的作用引发了人们对其作为冠状动脉疾病（CAD）生物标志物潜在意义的浓厚兴趣。在此，我们的目标是在一项病例对照关联研究中分析IL-33基因多态性是否与早发CAD相关。
采用5'核酸外切酶TaqMan分析法对1095例早发CAD患者和1118例对照进行4种IL-33多态性（rs7848215、rs16924144、rs16924159和rs7044343）的基因分型。
rs7044343 T等位基因与早发CAD风险降低显著相关（优势比[OR]=0.81，95%可信区间[CI]：0.69-0.97，显性模型P=0.020；OR=0.85，95%CI：0.75-0.96，加性模型P=0.019），并分别与中心性肥胖相关（OR=0.74，95%CI：0.58-0.93，显性模型P=0.0007）。当患者分为有和没有2型糖尿病（T2DM）的组时，rs7044343 T等位基因与无T2DM患者（OR=0.85，95%CI：0.73-0.99，加性模型P=0.038）和有T2DM患者（OR=0.61，95%CI：0.38-0.97，显性模型P=0.039；OR=0.69，95%CI：0.49-0.97，加性模型P=0.035）的早发CAD风险降低相关。为了确定rs7044343多态性的功能效应，在选定个体的单核细胞中测定了IL-33的产生。rs7044343 CC基因型个体的单核细胞产生的IL-33水平高于其他基因型个体的单核细胞。
结果表明，IL-33 rs7044343 T等位基因可能是早发CAD和中心性肥胖的易感标志物。rs7044343多态性可能参与调节IL-33的产生。
