OBJECTIVE: To examine sex differences in clinical, demographic, and genetic characteristics among a large cohort of patients with familial rheumatoid arthritis (RA). METHODS: We studied 1,004 affected members of 467 Caucasian multicase RA families recruited from the North American Rheumatoid Arthritis Consortium. Standardized information about demographic and clinical characteristics was collected from all patients. Affected individuals also underwent radiography of the hands and were genotyped for markers in the HLA region. Sex differences were assessed using contingency table analysis (for categorical variables) and Student's t-tests for (continuous variables), and by multivariate logistic and linear regression analysis. RESULTS: Male patients had a significantly later onset of RA, were more likely to be seropositive for RF, and had significantly higher titers of anti-cyclic citrullinated peptide (anti-CCP) antibodies compared with female patients, even after adjustment for covariates in multivariate analyses. Male patients were also significantly more likely to have a history of smoking and to be HLA-DRB1 shared epitope (SE) positive. Interestingly, female patients with an affected male sibling had significantly higher titers of anti-CCP antibodies and were more likely to be SE positive compared with female patients without affected male siblings. Multivariate analyses indicated that the presence of the SE did not fully explain the increased anti-CCP antibody titers observed in these families. CONCLUSION: Sex has an important influence on the disease phenotype in RA, including the age at disease onset and autoantibody production. Furthermore, families with affected male members are characterized by higher titers of autoantibodies, particularly anti-CCP antibodies. Our results indicate that these findings are not fully explained by differences in exposure to tobacco smoke, presence of the HLA-DRB1 SE, or other HLA region genetic variation. Thus, other genetic or nongenetic factors also contribute to sex differences in the RA phenotype.
OBJECTIVE: To examine sex differences in clinical, demographic, and genetic characteristics among a large cohort of patients with familial rheumatoid arthritis (RA). METHODS: We studied 1,004 affected members of 467 Caucasian multicase RA families recruited from the North American Rheumatoid Arthritis Consortium. Standardized information about demographic and clinical characteristics was collected from all patients. Affected individuals also underwent radiography of the hands and were genotyped for markers in the HLA region. Sex differences were assessed using contingency table analysis (for categorical variables) and Student's t-tests for (continuous variables), and by multivariate logistic and linear regression analysis. RESULTS: Male patients had a significantly later onset of RA, were more likely to be seropositive for RF, and had significantly higher titers of anti-cyclic citrullinated peptide (anti-CCP) antibodies compared with female patients, even after adjustment for covariates in multivariate analyses. Male patients were also significantly more likely to have a history of smoking and to be HLA-DRB1 shared epitope (SE) positive. Interestingly, female patients with an affected male sibling had significantly higher titers of anti-CCP antibodies and were more likely to be SE positive compared with female patients without affected male siblings. Multivariate analyses indicated that the presence of the SE did not fully explain the increased anti-CCP antibody titers observed in these families. CONCLUSION: Sex has an important influence on the disease phenotype in RA, including the age at disease onset and autoantibody production. Furthermore, families with affected male members are characterized by higher titers of autoantibodies, particularly anti-CCP antibodies. Our results indicate that these findings are not fully explained by differences in exposure to tobacco smoke, presence of the HLA-DRB1 SE, or other HLA region genetic variation. Thus, other genetic or nongenetic factors also contribute to sex differences in the RA phenotype.
Authors: Benjamin J Miriovsky; Kaleb Michaud; Geoffrey M Thiele; James R O'Dell; Grant W Cannon; Gail Kerr; J Steuart Richards; Dannette Johnson; Liron Caplan; Andreas Reimold; Roderick Hooker; Ted R Mikuls Journal: Ann Rheum Dis Date: 2010-05-03 Impact factor: 19.103
Authors: Isabela Goeldner; Thelma L Skare; Iara T de Messias Reason; Renato M Nisihara; Marília B Silva; Shirley R da Rosa Utiyama Journal: Clin Rheumatol Date: 2011-02-22 Impact factor: 2.980
Authors: Tuulikki Sokka; Sergio Toloza; Maurizio Cutolo; Hannu Kautiainen; Heidi Makinen; Feride Gogus; Vlado Skakic; Humeira Badsha; Tõnu Peets; Asta Baranauskaite; Pál Géher; Ilona Ujfalussy; Fotini N Skopouli; Maria Mavrommati; Rieke Alten; Christof Pohl; Jean Sibilia; Andrea Stancati; Fausto Salaffi; Wojciech Romanowski; Danuta Zarowny-Wierzbinska; Dan Henrohn; Barry Bresnihan; Patricia Minnock; Lene Surland Knudsen; Johannes Wg Jacobs; Jaime Calvo-Alen; Juris Lazovskis; Geraldo da Rocha Castelar Pinheiro; Dmitry Karateev; Daina Andersone; Sylejman Rexhepi; Yusuf Yazici; Theodore Pincus Journal: Arthritis Res Ther Date: 2009-01-14 Impact factor: 5.156