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学科主题: 临床医学
题名:
Genetic variant in IL33 is associated with susceptibility to rheumatoid arthritis
作者: Li, Chun1; Mu, Rong1; Guo, Jianping1; Wu, Xinyu1; Tu, Xin2; Liu, Xu1; Hu, Fanlei1; Guo, Shiwei1; Zhu, Jiaxin1; Xu, Huji3; Li, Zhanguo1
刊名: ARTHRITIS RESEARCH & THERAPY
发表日期: 2014
DOI: 10.1186/ar4554
卷: 16, 期:2
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Rheumatology
研究领域[WOS]: Rheumatology
关键词[WOS]: GENOME-WIDE ASSOCIATION ; ALZHEIMERS-DISEASE ; LARGE-SCALE ; IL-33 ; METAANALYSIS ; ASTHMA ; LOCI ; CYTOKINE ; RECEPTOR ; ST2
英文摘要:

Introduction: Interleukin (IL)-33 is a proinflammatory cytokine contributing to the pathogenesis of rheumatoid arthritis (RA). The gene encoding IL-33 may serve as a genetic factor and be associated with the risk of RA. To investigate the potential association between IL33 and RA, we performed a case-control study based on Chinese Han population.

Methods: A three-stage case-control study was performed. Two tag single-nucleotide polymorphisms (SNPs) (rs7044343 and rs10975514), mapping to the IL33 gene, were first genotyped in the discovery population. We further genotyped rs7044343 and rs10975514 in the validation and replication population. The associations between the two tag SNPs and phenotypic subgroups of RA and levels of serum IL-33 were assessed with a logistic regression model.

Results: In the discovery population, the CC genotype of rs7044343 was associated with RA patients (odds ratio (OR) = 0.777, 95% confidence interval (CI), 0.611 to 0.988; P = 0.040). After anti-citrullinated peptide antibody (ACPA) stratification, the CC genotype of rs7044343 was also shown to be a protective genotype in RA without ACPA (OR = 0.610; 95% CI, 0.379 to 0.982; P = 0.042). In the validation population and replication population, the association between rs7044343 and RA, especially ACPA-negative RA, was still significant. A meta-analysis of discovery, validation, and replication panels confirmed the association between CC genotype of rs7044343 and RA (P-combined = 0.0004; ORcombined = 0.77; 95% CI, 0.67 to 0.89). No evidence was found for heterogeneity between three sample sets (P-het = 0.99; I-2 = 0%). Similar results were also obtained in ACPA-negative RA (P-combined = 0.0002; ORcombined = 0.57; 95% CI, 0.43 to 0.77). No association was detected between rs10975514 polymorphism and RA susceptibility in the discovery and validation population. The serum levels of IL-33 were significantly lower in the patients with the rs7044343 CC genotype.

Conclusion: The CC genotype of rs7044343 in IL33 is associated with RA patients and downregulates IL-33 expression in RA.

语种: 英语
所属项目编号: 2010CB529100 ; 81072401 ; NCET-11-0181
项目资助者: Major State Basic Research Development Program of China (973 Program) ; National Natural Science Foundation of China ; Program for New Century Excellent Talents in University of China
WOS记录号: WOS:000338993100058
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67126
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Dept Rheumatol & Immunol, Beijing 100044, Peoples R China
2.Huazhong Univ Sci & Technol, Cardio X Inst, Ctr Human Genome Res, Key Lab Mol Biophys,Minist Educ,Coll Life Sci &, Wuhan 430074, Peoples R China
3.Second Mil Med Univ, Shanghai Changzheng Hosp, Dept Rheumatol & Immunol, Shanghai 200003, Peoples R China

Recommended Citation:
Li, Chun,Mu, Rong,Guo, Jianping,et al. Genetic variant in IL33 is associated with susceptibility to rheumatoid arthritis[J]. ARTHRITIS RESEARCH & THERAPY,2014,16(2).
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