Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

被引：171

作者：

Danoy, Patrick ^{[1
]}

Pryce, Karena ^{[1
]}

Hadler, Johanna ^{[1
]}

Bradbury, Linda A. ^{[1
]}

Farrar, Claire ^{[2
,3
]}

Pointon, Jennifer ^{[2
,3
]}

Ward, Michael ^{[4
]}

Weisman, Michael ^{[5
]}

Reveille, John D. ^{[6
]}

Wordsworth, B. Paul ^{[2
,3
]}

Stone, Millicent A. ^{[7
]}

Maksymowych, Walter P. ^{[8
]}

Rahman, Proton ^{[9
]}

Gladman, Dafna ^{[10
]}

Inman, Robert D. ^{[10
]}

Brown, Matthew A. ^{[1
,2
,3
]}

机构：

[1] Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia

[2] Univ Oxford, Inst Musculoskeletal Sci, Oxford, England

[3] Nuffield Orthopaed Ctr, NIHR Biomed Res Ctr, Oxford OX3 7LD, England

[4] NIAMSD, NIH, Bethesda, MD 20892 USA

[5] Cedars Sinai Med Ctr, Dept Med Rheumatol, Los Angeles, CA 90048 USA

[6] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA

[7] Univ Bath, Bath BA2 7AY, Avon, England

[8] Univ Alberta, Edmonton, AB, Canada

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

[10] Univ Toronto, Toronto, ON, Canada

来源：

PLOS GENETICS | 2010年 / 6卷 / 12期

基金：

英国医学研究理事会;

关键词：

GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; SUSCEPTIBILITY LOCI; PSORIASIS; SACROILIITIS; PREVALENCE; SCAN;

D O I：

10.1371/journal.pgen.1001195

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.66 x 10(-10), odds ratio (OR) = 0.74, 95% CI: 0.68-0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6 x 10(-4). OR = 0.86 (95% CI: 0.79-0.93); rs744166, P = 2.6 x 10(-5), OR = 0.84 (95% CI: 0.77-0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2 x 10(-5), OR = 0.65 (95% CI: 0.54-0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2 x 10(-5), OR = 0.83 (95% CI: 0.76-0.91)), CDKAL1 (rs6908425, P = 1.1 x 10(-4), OR = 0.82 (95% CI: 0.74-0.91)), LRRK2/MUC19 (rs11175593, P = 9.9 x 10(-5), OR = 1.92 (95% CI: 1.38-2.67)), and chr13q14 (rs3764147, P = 5.9 x 10(-4), OR = 1.19 (95% CI: 1.08-1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases.

引用

页码：1 / 5

页数：5

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