Open AccessFunctional polymorphism rs3783553 in the 3’-untranslated region of IL-1A increased the risk of ischemic stroke
Author(s) -
Peng Wang,
Qian He,
Chen Liu,
Shi Zhen He,
Shou Yan Zhu,
Ying Wen Li,
Wei Su,
Sheng Xiang,
Bo Zhao
Publication year - 2017
Publication title -
medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 148
eISSN - 1536-5964
pISSN - 0025-7974
DOI - 10.1097/md.0000000000008522
Subject(s) - medicine , odds ratio , genotype , confidence interval , logistic regression , allele , triglyceride , endocrinology , gastroenterology , cholesterol , genetics , gene , biology
Accumulating evidence indicates interleukin-1 (IL-1) is a critical mediator of inflammatory responses in ischemic stroke (IS). The aim of this study was to investigate whether rs3783553 in the 3’-untranslated region of IL-1A was associated with the risk of IS. In this hospital-based case-control study, we genotyped the rs3783553 using polymerase chain reaction in 316 patients with IS and 332 age, sex, and ethnicity-matched controls. Plasma level of IL-1α was measured by enzyme-linked immunosorbent assay. The relative luciferase activities were measured by the Dual Luciferase assay system. The presence of ins/ins genotype was associated with higher odds ratios (ORs) of IS compared with del/del genotype (ins/ins vs del/del: adjusted OR 1.77, 95% confidence interval [CI] 1.06–2.98; recessive model: adjusted OR 1.69, 95% CI 1.06–2.70). The higher risk of IS was also observed in allele comparison (adjusted OR 1.29, 95% CI 1.00–1.65). Multivariate logistic regression analysis showed that age, hypertension, total cholesterol, triglyceride, low-density lipoprotein, and rs3783553ins/ins genotypes were independent risk factors for IS. Plasma level of IL-1α was higher among IS patients compared with controls ( P = .03). Notably, IS patients with the TTCA/TTCA genotype had a higher level of IL-1α compared with those with the del/del genotype ( P = .01). Luciferase reporter assay showed that the vector containing the TTCA del allele exhibited a reduced transcriptional activity in the presence of miR-122 and miR-378. These findings indicate that IL-1A rs3783553 ins/ins genotype may increase the susceptibility to IS, possibly by interrupting the binding site of miR-122 and miR-378.