The association of PTPN22 rs2476601 with juvenile idiopathic arthritis is specific to females

被引：18

作者：

Chiaroni-Clarke, R. C. ^{[1
,2
]}

Li, Y. R. ^{[3
,4
]}

Munro, J. E. ^{[5
,6
]}

Chavez, R. A. ^{[1
,2
]}

Scurrah, K. J. ^{[7
]}

Pezic, A. ^{[8
]}

Akikusa, J. D. ^{[5
,6
]}

Allen, R. C. ^{[5
,6
]}

Piper, S. E. ^{[9
]}

Becker, M. L. ^{[10
]}

Thompson, S. D. ^{[11
]}

Lie, B. A. ^{[12
,13
]}

Flato, B. ^{[14
]}

Forre, O. ^{[14
]}

Punaro, M. ^{[15
]}

Wise, C. ^{[16
]}

Saffery, R. ^{[2
,17
]}

Finkel, T. H. ^{[18
,19
]}

Hakonarson, H. ^{[4
,19
]}

Ponsonby, A-L ^{[2
,8
]}

Ellis, J. A. ^{[1
,2
]}

机构：

[1] Murdoch Childrens Res Inst, Genes Environm & Complex Dis, Parkville, Vic 3052, Australia

[2] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia

[3] Univ Penn, Perelman Sch Med, Med Scientist Training Program, Philadelphia, PA 19104 USA

[4] Childrens Hosp Philadelphia, Abramson Res Ctr, Dept Pediat, Ctr Appl Genom, Philadelphia, PA 19104 USA

[5] Royal Childrens Hosp, Paediat Rheumatol Unit, Parkville, Vic 3052, Australia

[6] Murdoch Childrens Res Inst, Arthrit & Rheumatol Res, Parkville, Vic 3052, Australia

[7] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic 3052, Australia

[8] Murdoch Childrens Res Inst, Environm & Genet Epidemiol Res, Parkville, Vic 3052, Australia

[9] Monash Med Ctr, Monash Childrens Hosp, Dept Paediat Rheumatol, Clayton, Vic 3168, Australia

[10] Childrens Mercy Kansas City, Div Rheumatol & Clin Pharmacol, Med Toxicol & Therapeut Innovat, Kansas City, MO USA

[11] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA

[12] Oslo Univ Hosp, Dept Immunol, Oslo, Norway

[13] Univ Oslo, Oslo, Norway

[14] Oslo Univ Hosp, Dept Rheumatol, Oslo, Norway

[15] Texas Scottish Rite Hosp Children, Pediat Rheumatol, Dallas, TX 75219 USA

[16] Texas Scottish Rite Hosp Children, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Dallas, TX 75219 USA

[17] Murdoch Childrens Res Inst, Canc & Dis Epigenet, Parkville, Vic, Australia

[18] Nemours Childrens Hosp, Dept Pediat, Orlando, FL USA

[19] Univ Penn, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

来源：

GENES AND IMMUNITY | 2015年 / 16卷 / 07期

基金：

澳大利亚研究理事会; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

LYMPHOID TYROSINE PHOSPHATASE; DISEASE; VARIANT; RISK; AUTOIMMUNITY; POPULATION; CHILDHOOD; ALLELES; LOCI; GENE;

D O I：

10.1038/gene.2015.32

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

A preponderance of females develop autoimmune disease, including juvenile idiopathic arthritis (JIA), yet the reason for this bias remains elusive. Evidence suggests that genetic risk of disease may be influenced by sex. PTPN22 rs2476601 is associated with JIA and numerous other autoimmune diseases, and has been reported to show female-specific association with type 1 diabetes. We performed main effect and sex-stratified association analyses to determine whether a sex-specific association exists in JIA. As expected, rs2476601 was associated with JIA in our discovery (413 cases and 690 controls) and replication (1008 cases and 9284 controls) samples. Discovery sample sex-stratified analyses demonstrated an association specifically in females (odds ratio (OR) = 2.35, 95% confidence interval (CI) = 1.52-3.63, P = 0.00011) but not males (OR = 0.91, 95% CI = 0.52-1.60, P = 0.75). This was similarly observed in the replication sample. There was evidence for genotype-by-sex interaction (P-interaction = 0.009). The association between rs2476601 and JIA appears restricted to females, partly accounting for the predominance of females with this disease.

引用

页码：495 / 498

页数：4

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