A Candidate Gene Approach Identifies an IL33 Genetic Variant as a Novel Genetic Risk Factor for GCA

被引：16

作者：

Marquez, Ana ^{[1
,2
]}

Solans, Roser ^{[3
]}

Hernandez-Rodriguez, Jose ^{[4
]}

Cid, Maria C. ^{[4
]}

Castaneda, Santos ^{[5
]}

Ramentol, Marc ^{[3
]}

Rodriguez-Rodriguez, Luis ^{[6
]}

Narvaez, Javier ^{[7
]}

Blanco, Ricardo ^{[8
]}

Ortego-Centeno, Norberto ^{[2
]}

Palm, Oyvind ^{[9
]}

Diamantopoulos, Andreas P. ^{[10
]}

Braun, Niko ^{[11
]}

Moosig, Frank ^{[12
]}

Witte, Torsten ^{[13
]}

Beretta, Lorenzo ^{[14
]}

Lunardi, Claudio ^{[15
]}

Cimmino, Marco A. ^{[16
]}

Vaglio, Augusto ^{[17
]}

Salvarani, Carlo ^{[18
]}

Gonzalez-Gay, Miguel A. ^{[8
]}

Martin, Javier ^{[1
]}

机构：

[1] CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

[2] Hosp Clin San Cecilio, System Autoimmune Dis Unit, Granada, Spain

[3] Hosp Valle De Hebron, Dept Internal Med, Barcelona, Spain

[4] Univ Barcelona, Hosp Clin Barcelona, Ctr Recerca Biomed Cellex IDIBAPS, Vasculitis Res Unit,Dept Autoimmune & System Dis, Barcelona, Spain

[5] Hosp Princesa, IIS Princesa, Dept Rheumatol, Madrid, Spain

[6] Hosp Clin San Carlos, Dept Rheumatol, Madrid, Spain

[7] Hosp Univ Bellvitge IDIBELL, Dept Rheumatol, Barcelona, Spain

[8] Hosp Univ Marques de Valdecilla, IFIMAV, Dept Rheumatol, Santander, Spain

[9] Oslo Univ Hosp, Rikshosp, Dept Rheumatol, Oslo, Norway

[10] Hosp Southern Norway Trust, Dept Rheumatol, Kristiansand, Norway

[11] Robert Bosch Krankenhaus, Dept Internal Med, Div Nephrol, Stuttgart, Germany

[12] Univ Lubeck, Dept Clin Immunol & Rheumatol, Bad Bramstedt, Germany

[13] Hannover Med Sch, Hannover, Germany

[14] Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Referral Ctr Syst Autoimmune Dis, Milan, Italy

[15] Univ Verona, Dept Med, I-37100 Verona, Italy

[16] Univ Genoa, Dept Internal Med, Acad Unit Clin Rheumatol, I-16126 Genoa, Italy

[17] Univ Hosp Parma, Dept Clin Med Nephrol & Hlth Sci, Parma, Italy

[18] Azienda Osped ASMN, Ist Ricovero & Cura Carattere Sci, Unita Operat Reumatol, Reggio Emilia, Italy

来源：

PLOS ONE | 2014年 / 9卷 / 11期

关键词：

GIANT-CELL ARTERITIS; GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; ADHESION MOLECULES; MAST-CELLS; IL-33; ASTHMA; METAANALYSIS; VARIANTS; DISEASE;

D O I：

10.1371/journal.pone.0113476

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：7

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