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X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren’s Syndrome

Liu, Ke ; Kurien, Biji T. ; Zimmerman, Sarah L. ; Kaufman, Kenneth M. ; Taft, Diana H. ; Kottyan, Leah C. ; Lazaro, Sara ; Weaver, Carrie A. ; Ice, John A. ; Adler, Adam J. ; Chodosh, James ; Radfar, Lida ; Rasmussen, Astrid ; Stone, Donald U. ; Lewis, David M. ; Li, Shibo ; Koelsch, Kristi A. ; Igoe, Ann ; Talsania, Mitali ; Kumar, Jay ; Maier-Moore, Jacen S. ; Harris, Valerie M. ; Gopalakrishnan, Rajaram ; Jonsson, Roland ; Lessard, James A. ; Lu, Xianglan ; Gottenberg, Jacques-Eric ; Anaya, Juan-Manuel ; Cunninghame-Graham, Deborah S. ; Huang, Andrew J. W. ; Brennan, Michael T. ; Hughes, Pamela ; Illei, Gabor G. ; Miceli-Richard, Corinne ; Keystone, Edward C. ; Bykerk, Vivian P. ; Hirschfield, Gideon ; Xie, Gang ; Ng, Wan-Fai ; Nordmark, Gunnel ; Eriksson, Per ; Omdal, Roald ; Rhodus, Nelson L. ; Rischmueller, Maureen ; Rohrer, Michael ; Segal, Barbara M. ; Vyse, Timothy J. ; Wahren-Herlenius, Marie ; Witte, Torsten ; Pons-Estel, Bernardo ; Alarcon-Riquelme, Marta E. ; Guthridge, Joel M. ; James, Judith A. ; Lessard, Christopher J. ; Kelly, Jennifer A. ; Thompson, Susan D. ; Gaffney, Patrick M. ; Montgomery, Courtney G. ; Edberg, Jeffrey C ; Kimberly, Robert P ; Alarcón, Graciela S. ; Langefeld, Carl L. ; Gilkeson, Gary S. ; Kamen, Diane L. ; Tsao, Betty P. ; McCune, W. Joseph ; Salmon, Jane E. ; Merrill, Joan T. ; Weisman, Michael H ; Wallace, Daniel J ; Utset, Tammy O ; Bottinger, Erwin P. ; Amos, Christopher I. ; Siminovitch, Katherine A. ; Mariette, Xavier ; Sivils, Kathy L. ; Harley, John B. ; Scofield, R. Hal

Arthritis & rheumatology (Hoboken, N.J.), 2016-05, Vol.68 (5), p.1290-1300 [Periódico revisado por pares]

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Título:
X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren’s Syndrome
Autor: Liu, Ke ; Kurien, Biji T. ; Zimmerman, Sarah L. ; Kaufman, Kenneth M. ; Taft, Diana H. ; Kottyan, Leah C. ; Lazaro, Sara ; Weaver, Carrie A. ; Ice, John A. ; Adler, Adam J. ; Chodosh, James ; Radfar, Lida ; Rasmussen, Astrid ; Stone, Donald U. ; Lewis, David M. ; Li, Shibo ; Koelsch, Kristi A. ; Igoe, Ann ; Talsania, Mitali ; Kumar, Jay ; Maier-Moore, Jacen S. ; Harris, Valerie M. ; Gopalakrishnan, Rajaram ; Jonsson, Roland ; Lessard, James A. ; Lu, Xianglan ; Gottenberg, Jacques-Eric ; Anaya, Juan-Manuel ; Cunninghame-Graham, Deborah S. ; Huang, Andrew J. W. ; Brennan, Michael T. ; Hughes, Pamela ; Illei, Gabor G. ; Miceli-Richard, Corinne ; Keystone, Edward C. ; Bykerk, Vivian P. ; Hirschfield, Gideon ; Xie, Gang ; Ng, Wan-Fai ; Nordmark, Gunnel ; Eriksson, Per ; Omdal, Roald ; Rhodus, Nelson L. ; Rischmueller, Maureen ; Rohrer, Michael ; Segal, Barbara M. ; Vyse, Timothy J. ; Wahren-Herlenius, Marie ; Witte, Torsten ; Pons-Estel, Bernardo ; Alarcon-Riquelme, Marta E. ; Guthridge, Joel M. ; James, Judith A. ; Lessard, Christopher J. ; Kelly, Jennifer A. ; Thompson, Susan D. ; Gaffney, Patrick M. ; Montgomery, Courtney G. ; Edberg, Jeffrey C ; Kimberly, Robert P ; Alarcón, Graciela S. ; Langefeld, Carl L. ; Gilkeson, Gary S. ; Kamen, Diane L. ; Tsao, Betty P. ; McCune, W. Joseph ; Salmon, Jane E. ; Merrill, Joan T. ; Weisman, Michael H ; Wallace, Daniel J ; Utset, Tammy O ; Bottinger, Erwin P. ; Amos, Christopher I. ; Siminovitch, Katherine A. ; Mariette, Xavier ; Sivils, Kathy L. ; Harley, John B. ; Scofield, R. Hal
É parte de: Arthritis & rheumatology (Hoboken, N.J.), 2016-05, Vol.68 (5), p.1290-1300
Descrição: OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
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X Chromosome Dose and Sex Bias in Autoimmune Diseases: Increased 47,XXX in Systemic Lupus Erythematosus and Sjögren’s Syndrome

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