A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA
PLOS ONE
Authors: Marquez, Ana; Solans, Roser; Hernandez-Rodriguez, Jose; Cid, Maria C.; Castaneda, Santos; Ramentol, Marc; Rodriguez-Rodriguez, Luis; Narvaez, Javier; Blanco, Ricardo; Ortego-Centeno, Norberto; Palm, Oyvind; Diamantopoulos, Andreas P.; Braun, Niko; Moosig, Frank; Witte, Torsten; Beretta, Lorenzo; Lunardi, Claudio; Cimmino, Marco A.; Vaglio, Augusto; Salvarani, Carlo; Gonzalez-Gay, Miguel A.; Martin, Javier
Abstract
Introduction: Increased expression of IL-33 and its receptor ST2, encoded by the IL1RL1 gene, has been detected in the inflamed arteries of giant cell arteritis (GCA) patients. The aim of the present study was to investigate for the first time the potential influence of the IL33 and IL1RL1 loci on GCA predisposition. Methods: A total of 1,363 biopsy-proven GCA patients and 3,908 healthy controls from four European cohorts (Spain, Italy, Germany and Norway) were combined in a meta-analysis. Six genetic variants: rs3939286, rs7025417 and rs7044343, within the IL33 gene, and rs2058660, rs2310173 and rs13015714, within the IL1RL1 gene, previously associated with immunerelated diseases, were genotyped using predesigned TaqMan assays. Results: A consistent association between the rs7025417 polymorphism and GCA was evident in the overall meta-analysis, under both allele (P-MH = 0.041, OR = 0.88, CI 95% 0.78-0.99) and recessive (P-MH = 3.40E-03, OR = 0.53, CI 95% 0.35-0.80) models. No statistically significant differences between allele or genotype frequencies for the other IL33 and IL1RL1 genetic variants were detected in this pooled analysis. Conclusions: Our results clearly evidenced the implication of the IL33 rs7025417 polymorphism in the genetic network underlying GCA.
Association of Common Variants in the IL-33/ST2 Axis with Ischemic Stroke
CURRENT NEUROVASCULAR RESEARCH
Authors: Li, Shuo; Wang, Zhijie; Liu, Xinjing; Li, Yuanzhe; Shi, Changhe; Wu, Jun; Sun, Shilei; Li, Yusheng; Li, Shaohua; Xu, Yuming; Song, Bo
Abstract
Background: Recent studies have reported that the levels of serum interleukin-33 (IL33) and its receptor, suppression of tumorigenicity 2 (ST2), are potential biomarkers for susceptibility of cardiovascular diseases. However, the genetic association of the IL-33/ST2 axis with cardiovascular diseases remains controversial. Objective: We aimed to investigate the association between common variants in the IL-33/ST2 axis and ischemic stroke in the Han Chinese population. Methods: We consecutively enrolled 1166 patients with ischemic stroke and 1079 age- and gender-matched controls. Eight single nucleotide polymorphisms (SNPs) within IL-33/ST2 axis were genotyped using the improved Multiple Ligase Detection Reaction platform. We analyzed the association between the tested SNPs and ischemic stroke at both the genotype and haplotype levels. Results: Binary logistic regression analysis indicated that rs10435816 (additive model: odds ratio [OR]=0.72, 95% confidence interval [CI], 0.54-0.95; recessive model: 012=0.72, 95%CI, 0.560.94) was associated with a decreased risk of ischemic stroke after adjustment of confounding factors. Subgroup analysis indicated that rs10435816 (additive model: 012=0.61, 95%CI, 0.41-0.89; recessive model: 012=0.56, 95%CI, 0.40-0.80), rs7025417 (additive model: 012=0.57, 95%CI, 0.39-0.83), rs11792633 (additive model: 012=0.66, 95%CI, 0.46-0.95; recessive model: 012=0.67, 95%CI, 0.49-0.93), and rs7044343 (additive model: 012=0.69, 95%CI, 0.48-0.97; recessive model: 012=0.67, 95%CI, 0.49-0.91) were associated with a decreased risk of large-artery atherosclerosis stroke after adjustment of confounding factors. Conclusion: Our findings suggested an association between common variants n the IL-33/ST2 axis and a decreased risk of ischemic stroke in the Han Chinese population.