The shared epitope (SE) hypothesis was initially proposed to explain genetic susceptibility to rheumatoid arthritis (RA), but further study suggests that the primary role of the SE may be in the development of more severe manifestations of the disease. Despite numerous studies over the past decade, the true relationship of the SE and RA severity remains unclear. Difficulty in clarifying this relationship is likely due to differences in the populations studied: those of ethnicity, clinical factors and the particular SE allele inherited as well as the small number of patients in individual studies. In order to examine the association thoroughly, evaluation of a large, clinically and ethnically diverse population is required, and to date, no attempt has been made to initiate such a project. The goal of this proposal is to precisely define the role of the SE in severity of RA among patients with a broad range of ethnic and clinical characteristics. In order to accomplish this goal we have the following specific aim for this project: 1. To perform a meta-analysis of the association of the SE and severity of RA utilizing individual level data obtained from researchers worldwide. Because the relationship between genotype and RA severity appears to vary according to characteristics of the patients, such as ethnicity and gender, the importance of these covariates will be examined. The association will be analyzed in terms of three genetic models: presence or absence of the SE, SE dosage (0, 1, or 2 alleles), and by the specific SE genotype inherited. Severity of RA will be defined by the following outcome measures: seropositivity, presence of radiographic erosions, disease course, requirement for joint surgery, and presence of nodules or other extra- articular manifestations. This proposal of a meta-analysis with use of individual level data will allow us to more clearly define the precise relationship between the SE and RA severity and has the ability to provide genetic predictors of prognosis for RA patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Comprehensive Center (P60)
Project #
5P60AR020684-24
Application #
6422925
Study Section
Special Emphasis Panel (ZAR1)
Project Start
1977-09-15
Project End
2002-12-31
Budget Start
Budget End
Support Year
24
Fiscal Year
2001
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Briggs, F B S; Ramsay, P P; Madden, E et al. (2010) Supervised machine learning and logistic regression identifies novel epistatic risk factors with PTPN22 for rheumatoid arthritis. Genes Immun 11:199-208
Yazdany, Jinoos; Yelin, Edward (2010) Health-related quality of life and employment among persons with systemic lupus erythematosus. Rheum Dis Clin North Am 36:15-32, vii
Janssens, A Cecile J W; Steyerberg, Ewout W; Jiang, Yebin et al. (2006) Value of the HLA-DRB1 shared epitope for predicting radiographic damage in rheumatoid arthritis depends on the individual patient risk profile. J Rheumatol 33:2383-9
Katz, Patricia P (2006) Childbearing decisions and family size among women with rheumatoid arthritis. Arthritis Rheum 55:217-23
Yelin, Edward H; Trupin, Laura S; Katz, Patricia P (2005) Impact of managed care on the use of biologic agents for rheumatoid arthritis. Arthritis Rheum 53:423-30
Katz, Patricia P (2005) Use of self-management behaviors to cope with rheumatoid arthritis stressors. Arthritis Rheum 53:939-49
von Scheven, E; Elder, M E (2005) Association between beta2-glycoprotein I gene polymorphisms and pediatric SLE and antiphospholipid antibodies. Lupus 14:440-4
Yang, Nan; Li, Hongzhe; Criswell, Lindsey A et al. (2005) Examination of ancestry and ethnic affiliation using highly informative diallelic DNA markers: application to diverse and admixed populations and implications for clinical epidemiology and forensic medicine. Hum Genet 118:382-92
Seldin, Michael F; Morii, Takanobu; Collins-Schramm, Heather E et al. (2004) Putative ancestral origins of chromosomal segments in individual african americans: implications for admixture mapping. Genome Res 14:1076-84
Chang, Wenhan; Shoback, Dolores (2004) Extracellular Ca2+-sensing receptors--an overview. Cell Calcium 35:183-96

Showing the most recent 10 out of 111 publications