Functional polymorphism rs3783553 in the 3’-untranslated region of IL-1A increased the risk of ischemic stroke

Abstract

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.

Genetic predisposition and bioinformatics analysis of ATP-sensitive potassium channels polymorphisms with the risks of elevated apolipoprotein B serum levels and its related arteriosclerosis cardiovascular disease

“…Our findings were in favor of recent observations that reported the DE miRs ( e.g. , miR-17-5p [ 26 ], miR-210 [ 27 ], miR-218 [ 28 ], miR-422a [ 29 ], miR-497 [ 30 ], miR-4429 [ 31 ], miR-208 family [ 25 ], miR-320 family [ 31 ] and miR-378 family [ 32 ]) in patients with IS, and part of them could be as markers for an early diagnosis of stroke. In a 4-year prospective study for identifying the markers of CAS related IS, Gacon J et al [ 25 ] reported that elevated miR-208b-3p level were obviously linked to cerebral ischaemic events risk.…”

Variants in genes related to inflammation and endothelial function can increase the risk for carotid atherosclerosis in southwestern China

“…After cerebral ischemia, IL-1a express in microglia, astrocytes, and endothelial cells, inducing activation of astrocytes and endothelial cells and promoting formation of tube-like structure that is an important hallmark of angiogenesis, knockout IL-1a in mice can reduce ischemic damage ( 27 , 28 ). Polymorphisms in IL1A gene may increase the risk of ischemic stroke ( 29 ). In this study, we also revealed polymorphisms in IL1A were associated with carotid atherosclerosis.…”

A 3′ Untranslated Region Polymorphism of <b><i>CTNNB1</i></b> (Rs2953) Alters MiR-3161 Binding and Affects the Risk of Ischemic Stroke and Coronary Artery Disease in Chinese Han Population

“…For example, the C-to-T substitution in polymorphism rs3735590 disrupts the binding affinity between miR-616 and PON1 , causing the overexpression of gene PON1 associated with IS risk [44]. IL-1A rs3783553 TTCA ins allele located in the 3′UTR disrupts the binding of miR-122 and miR-378 to IL-1A , thereby promoting the upregulation of the plasma level of IL-1a and finally increased IS risk [21]. The minor allele T, as the ancestral allele of rs2953, introduced a miR-3161 binding site, whereas the derived G allele was discovered to abolish the miR-3161 regulation to the CTNNB1 gene.…”

“…For example, miR-1203 binds to polymorphism rs868014 located on the 3′UTR of MTHFR, which is related not only to the risk but also to the short-term outcome of IS [20]. Similarly, rs3783553 in the 3′UTR of IL-1A alters susceptibility to IS by interrupting the bind-ing site of miR-122 and miR-378 [21]. It is also well recognized that polymorphisms in the 3′UTR can both positively and negatively affect miRNA-mediated regulation of CAD [22].…”