Title |
X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased Prevalence of 47,XXX in Systemic Lupus Erythematosus and Sjögren's Syndrome
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Published in |
Arthritis & Rheumatology, April 2016
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DOI | 10.1002/art.39560 |
Pubmed ID | |
Authors |
Ke Liu, Biji T Kurien, Sarah L Zimmerman, Kenneth M Kaufman, Diana H Taft, Leah C Kottyan, Sara Lazaro, Carrie A Weaver, John A Ice, Adam J Adler, James Chodosh, Lida Radfar, Astrid Rasmussen, Donald U Stone, David M Lewis, Shibo Li, Kristi A Koelsch, Ann Igoe, Mitali Talsania, Jay Kumar, Jacen S Maier-Moore, Valerie M Harris, Rajaram Gopalakrishnan, Roland Jonsson, James A Lessard, Xianglan Lu, Jacques-Eric Gottenberg, Juan-Manuel Anaya, Deborah S Cunninghame-Graham, Andrew J W Huang, Michael T Brennan, Pamela Hughes, Gabor G Illei, Corinne Miceli-Richard, Edward C Keystone, Vivian P Bykerk, Gideon Hirschfield, Gang Xie, Wan-Fai Ng, Gunnel Nordmark, Per Eriksson, Roald Omdal, Nelson L Rhodus, Maureen Rischmueller, Michael Rohrer, Barbara M Segal, Timothy J Vyse, Marie Wahren-Herlenius, Torsten Witte, Bernardo Pons-Estel, Marta E Alarcon-Riquelme, Joel M Guthridge, Judith A James, Christopher J Lessard, Jennifer A Kelly, Susan D Thompson, Patrick M Gaffney, Courtney G Montgomery, Jeffrey C Edberg, Robert P Kimberly, Graciela S Alarcón, Carl L Langefeld, Gary S Gilkeson, Diane L Kamen, Betty P Tsao, W Joseph McCune, Jane E Salmon, Joan T Merrill, Michael H Weisman, Daniel J Wallace, Tammy O Utset, Erwin P Bottinger, Christopher I Amos, Katherine A Siminovitch, Xavier Mariette, Kathy L Sivils, John B Harley, R Hal Scofield |
Abstract |
More than 80% of autoimmune disease is female dominant, but the mechanism for this female bias is poorly understood. We suspected an X chromosome dose effect and hypothesized that trisomy X (47,XXX, 1 in ∼1,000 live female births) would be increased in female predominant diseases (e.g. systemic lupus erythematosus [SLE], primary Sjögren's syndrome [SS], primary biliary cirrhosis [PBC] and rheumatoid arthritis [RA]) compared to diseases without female predominance (sarcoidosis) and controls. We identified 47,XXX subjects using aggregate data from single nucleotide polymorphism (SNP) arrays and confirmed, when possible, by fluorescent in situ hybridization (FISH) or quantitative polymerase chain reaction (q-PCR). We found 47,XXX in seven of 2,826 SLE and three of 1,033 SS female patients, but only in two of the 7,074 female controls (p=0.003, OR=8.78, 95% CI: 1.67-86.79 and p=0.02, OR=10.29, 95% CI: 1.18-123.47; respectively). One 47,XXX subject was present for ∼404 SLE women and ∼344 SS women. 47,XXX was present in excess among SLE and SS subjects. The estimated prevalence of SLE and SS in women with 47,XXX was respectively ∼2.5 and ∼2.9 times higher than in 46,XX women and ∼25 and ∼41 times higher than in 46,XY men. No statistically significant increase of 47,XXX was observed in other female-biased diseases (PBC or RA), supporting the idea of multiple pathways to sex bias in autoimmunity. This article is protected by copyright. All rights reserved. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 60% |
Unknown | 2 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 4 | 80% |
Scientists | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 143 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 20 | 14% |
Student > Bachelor | 17 | 12% |
Researcher | 15 | 10% |
Student > Master | 10 | 7% |
Professor | 8 | 6% |
Other | 28 | 20% |
Unknown | 45 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 41 | 29% |
Biochemistry, Genetics and Molecular Biology | 21 | 15% |
Agricultural and Biological Sciences | 10 | 7% |
Immunology and Microbiology | 7 | 5% |
Neuroscience | 3 | 2% |
Other | 8 | 6% |
Unknown | 53 | 37% |