Prospective meta-analysis of interleukin 1 gene complex polymorphisms confirms associations with ankylosing spondylitis

被引：97

作者：

Sims, A-M ^{[1
,2
]}

Timms, A. E. ^{[2
]}

Bruges-Armas, J. ^{[3
]}

Burgos-Vargas, R. ^{[4
,5
]}

Chou, C-T ^{[6
]}

Doan, T. ^{[1
]}

Dowling, A. ^{[1
]}

Fialho, R. N. ^{[3
]}

Gergely, P. ^{[7
]}

Gladman, D. D. ^{[8
]}

Inman, R. ^{[8
]}

Kauppi, M. ^{[9
]}

Kaarela, K. ^{[9
]}

Laiho, K. ^{[9
,10
]}

Maksymowych, W. ^{[11
]}

Pointon, J. J.

Rahman, P. ^{[12
]}

Reveille, J. D. ^{[13
]}

Sorrentino, R. ^{[14
]}

Tuomilehto, J. ^{[15
]}

Vargas-Alarcon, G. ^{[16
]}

Wordsworth, B. P. ^{[1
]}

Xu, H. ^{[17
,18
]}

Brown, M. A. ^{[1
,2
]}

机构：

[1] Univ Queensland, Diamantina Inst Canc Immunol & Metab Med, Brisbane, Qld, Australia

[2] Univ Oxford, Botnar Res Ctr, Oxford, England

[3] Univ Porto, SEEBMO Azores, IBMC Mol & Cellular Biol Inst, P-4100 Oporto, Portugal

[4] Univ Nacl Autonoma Mexico, Mexico City 04510, DF, Mexico

[5] Hosp Gen Mexico City, Mexico City, DF, Mexico

[6] Vet Gen Hosp, Taipei, Taiwan

[7] Natl Inst Rheumatism & Physiotherapy, Budapest, Hungary

[8] Univ Toronto, Toronto, ON, Canada

[9] Rheumatism Fdn Hosp, SF-18120 Heinola, Finland

[10] Tampere Univ, Sch Med, Dept Musculoskeletal Med, FIN-33101 Tampere, Finland

[11] Univ Alberta, Edmonton, AB, Canada

[12] Mem Univ Newfoundland, St John, NF, Canada

[13] Univ Texas Austin, Austin, TX 78712 USA

[14] Univ Roma La Sapienza, Dept Cell Biol & Dev, Rome, Italy

[15] Natl Publ Hlth Inst, Helsinki, Finland

[16] Inst Nacl Cardiol Ignacio Chavez, Mexico City, DF, Mexico

[17] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[18] Second Mil Med Univ, Changzheng Hosp, Shanghai, Peoples R China

来源：

ANNALS OF THE RHEUMATIC DISEASES | 2008年 / 67卷 / 09期

关键词：

D O I：

10.1136/ard.2007.081364

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives: The aim of the current study was to determine the contribution of interleukin (IL) 1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide. Methods: Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis. Results: Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%. Conclusions: This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.

引用

页码：1305 / 1309

页数：5

共 24 条

[1]

Brown MA, 1998, ARTHRITIS RHEUM, V41, P588, DOI 10.1002/1529-0131(199804)41:4<588::AID-ART5>3.3.CO

[2]

2-S

[3] Replication of association of IL1 gene complex members with ankylosing spondylitis in Taiwanese Chinese [J].

Chou, C. -T. ;

Timms, A. E. ;

Wei, J. C. C. ;

Tsai, W. C. ;

Wordsworth, B. P. ;

Brown, M. A. .

ANNALS OF THE RHEUMATIC DISEASES, 2006, 65 (08) :1106-1109

[4] Open label trial of anakinra in active ankylosing spondylitis over 24 weeks [J].

Haibel, H ;

Rudwaleit, M ;

Listing, J ;

Sieper, J .

ANNALS OF THE RHEUMATIC DISEASES, 2005, 64 (02) :296-298

[5] Quantifying heterogeneity in a meta-analysis [J].

Higgins, JPT ;

Thompson, SG .

STATISTICS IN MEDICINE, 2002, 21 (11) :1539-1558

[6] Interleukin-1 induces pro-mineralizing activity of cartilage tissue transglutaminase and factor XIIIa [J].

Johnson, K ;

Hashimoto, S ;

Lotz, M ;

Pritzker, K ;

Terkeltaub, R .

AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (01) :149-163

[7] Contribution of single nucleotide polymorphisms of the IL1A gene to the cleavage of precursor IL-1α and its transcription activity [J].

Kawaguchi, Yasushi ;

Tochimoto, Akiko ;

Hara, Masako ;

Kawamoto, Manabu ;

Sugiura, Tomoko ;

Saito, Seiji ;

Kamatani, Naoyuki .

IMMUNOGENETICS, 2007, 59 (06) :441-448

[8] Association of the IL1 gene cluster with susceptibility to ankylosing spondylitis -: An analysis of three Canadian populations [J].

Maksymowych, WP ;

Rahman, P ;

Reeve, JP ;

Gladman, DD ;

Peddle, L ;

Inman, RD .

ARTHRITIS AND RHEUMATISM, 2006, 54 (03) :974-985

[9]

Maksymowych WP, 2005, ARTHRITIS RHEUM-US, V52, pS692

[10] High-throughput single-nucleotide polymorphism analysis of the IL1RN locus in patients with ankylosing spondylitis by matrix-assisted laser desorption ionization-time-of-flight mass spectrometry [J].

Maksymowych, WP ;

Reeve, JP ;

Reveille, JD ;

Akey, JM ;

Buenviaje, H ;

O'Brien, L ;

Peloso, PM ;

Thomson, GT ;

Jin, L ;

Russell, AS .

ARTHRITIS AND RHEUMATISM, 2003, 48 (07) :2011-2018

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