Inflammation damages the joints of rheumatoid arthritis (RA) patients. They experience pain, loss of motion, physical disability and a shortened lifespan. Despite estimates suggesting Mexican Americans (MA) may be more susceptible to RA than other major U.S. ethnic groups, little is known about the clinical expression or outcome in RA in MA. Our goals are to identify optimal points for intervention to retard disablement in RA, and to understand the mechanisms of ethnic disparities. Toward these goals, we developed a novel biopsychosocial model of disability in RA, which guided our study of a multiethnic cohort of 779 RA patients. During the initial funding period from 1999 to 2005, we followed the cohort for 3,967 patient-years. Key findings from the initial period that we aim to study further include: First, a significant ethnic disparity in the clinical expression of RA, MA having more severe manifestations at every stage of the disablement process;and second, extreme variation among the patients in the accrual of joint damage.
Our Specific Aims are: 1) To identify gene variants (single nucleotide polymorphisms, or SNPs), associated with the joint damage phenotype in RA, and to examine their downstream influence on the disablement process;2) To examine the extent to which ethnic variation in the disablement process in RA is explained by genetic and environmental factors;and 3) To examine the influence of ethnicity, genetic and environmental factors on survival in RA. We will study MA and non-Hispanic White (NHW) members of the original RA cohort (n=655) and will recruit additional patients for a combined sample size of 500 MA and 500 NHW RA patients. We will follow patients longitudinally to evaluate the process of disablement, and survival. We will study 25 carefully selected candidate genes found previously to be associated with RA susceptibility and/or severity. In each gene, we will genotype an average of 20 SNPs, selected to capture the largest amount of regional genetic information, or for their potential to alter gene function. We will use Bayesian Quantitative Trait Nucleotide analysis (BQTN) to identify SNPs associated with joint damage. This research will advance current understanding of the genotype-phenotype relationship in RA, and of how genes and the environment contribute to ethnic disparities in the disablement process. SNPs associated with RA damage may be useful for risk stratification of patients, and may contribute to the discovery of novel targets for RA treatments.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD037151-10
Application #
8112472
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Quatrano, Louis A
Project Start
1999-08-01
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2011
Total Cost
$553,634
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Molina, Emily; del Rincon, Inmaculada; Restrepo, Jose Felix et al. (2015) Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on death certificates. BMC Musculoskelet Disord 16:277
Arya, Rector; Del Rincon, Inmaculada; Farook, Vidya S et al. (2015) Genetic Variants Influencing Joint Damage in Mexican Americans and European Americans With Rheumatoid Arthritis. Genet Epidemiol 39:678-88
Molina, Emily; Del Rincon, Inmaculada; Restrepo, Jose Felix et al. (2015) Association of socioeconomic status with treatment delays, disease activity, joint damage, and disability in rheumatoid arthritis. Arthritis Care Res (Hoboken) 67:940-6
del Rincón, Inmaculada; Polak, Joseph F; O'Leary, Daniel H et al. (2015) Systemic inflammation and cardiovascular risk factors predict rapid progression of atherosclerosis in rheumatoid arthritis. Ann Rheum Dis 74:1118-23
Restrepo, José Félix; del Rincón, Inmaculada; Battafarano, Daniel F et al. (2015) Clinical and laboratory factors associated with interstitial lung disease in rheumatoid arthritis. Clin Rheumatol 34:1529-36
del Rincón, Inmaculada; Battafarano, Daniel F; Restrepo, Jose F et al. (2014) Glucocorticoid dose thresholds associated with all-cause and cardiovascular mortality in rheumatoid arthritis. Arthritis Rheumatol 66:264-72
Molina, Emily; Haas, Roy; del Rincon, Inmaculada et al. (2014) Does the ""Hispanic paradox"" occur in rheumatoid arthritis? Survival data from a multiethnic cohort. Arthritis Care Res (Hoboken) 66:972-9
Evans, Matthew R; Escalante, Agustín; Battafarano, Daniel F et al. (2011) Carotid atherosclerosis predicts incident acute coronary syndromes in rheumatoid arthritis. Arthritis Rheum 63:1211-20
Roldan, Jose F; Escalante, Agustin; del Rincon, Inmaculada (2008) Impaired arterial function associated with thinning of cortical bone in rheumatoid arthritis. Arthritis Rheum 59:523-30
Del Rincon, Inmaculada; O'Leary, Daniel H; Freeman, Gregory L et al. (2007) Acceleration of atherosclerosis during the course of rheumatoid arthritis. Atherosclerosis 195:354-60

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