Systemic Lupus Erythmatosus and Other Autoimmune Disease

Cooper, Glinda S.

Abstract

This project involves my work with lupus and other autoimmune diseases. The role of genetic susceptibility in lupus has been extensively examined, but the idea that lupus can be explained solely by genetics is not supported by recent studies. The concordance rate among monozygotic twins is currently thought to be 25% - 33%, substantially lower than the 75% figure derived from small studies subject to substantial selection bias published in the 1960s and 1970s. There is a clear need to look beyond genetics in order to understand this and other autoimmune diseases. My work represents a broader approach to studying lupus. It is an approach that is based on the often-cited idea that lupus involves a combination of, and interaction between, genetic and environmental factors. This work focuses on genetic factors and on measures of endogenous hormonal exposures, exogenous sources of estrogen, and on environmental exposures that may affect the risk of lupus and of other autoimmune diseases. Importantly, I have used sound methodologic designs to develop the studies within this research program, including population-based approaches to identifying patients and appropriate comparison groups. I have also developed innovative approaches to exposure assessment within the context of case-control studies. The specific studies that have been completed or are currently underway within this project include: 1) The Carolina Lupus Study - the first large, population-based case-control study of genetic, hormonal, and environmental risk factors for lupus in the US 2) Dietary Risk Factors for Lupus - a prospective analysis using data from the Nurses' Health Study (I and II) 3) Parity and Risk of Systemic Sclerosis - an analysis using a unique resource, the hospitalization and pregnancy registries covering the entire population of Sweden 4) Pesticide Exposure and Risk of Rheumatoid Arthritis - an analysis using the Agricultural Health Study cohort of spouses of licensed pesticide applicators 5) Immunological Effects of DDE - an analysis of serum DDE levels in relation to immunoglobulin and autoantibodies among African-American farmers

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Environmental Health Sciences (NIEHS)
• Type: Intramural Research (Z01)
• Project #: 1Z01ES049023-08
• Application #: 7007390
• Study Section: Epidemiology and Biometry Training Committee (EB)
• Support Year: 8
• Fiscal Year: 2004

Institution

• Name: U.S. National Inst of Environ Hlth Scis
• Country: United States

Publications

Cooper, Glinda S; Bynum, Milele L K; Somers, Emily C (2009) Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 33:197-207

Cooper, Glinda S; Treadwell, Edward L; St Clair, E William et al. (2007) Sociodemographic associations with early disease damage in patients with systemic lupus erythematosus. Arthritis Rheum 57:993-9

Calvo-Alen, J; Alarcon, G S; Campbell Jr, R et al. (2005) Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients. Rheumatology (Oxford) 44:1186-9

De Roos, Anneclaire J; Cooper, Glinda S; Alavanja, Michael C et al. (2005) Rheumatoid arthritis among women in the Agricultural Health Study: risk associated with farming activities and exposures. Ann Epidemiol 15:762-70

Szalai, A J; Wu, J; Lange, E M et al. (2005) Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level. J Mol Med 83:440-7

Parks, Christine G; Cooper, Glinda S; Hudson, Lori L et al. (2005) Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype. Arthritis Rheum 52:1148-59

Cooper, Glinda S; Treadwell, Edward L; Dooley, Mary Anne et al. (2004) N-acetyl transferase genotypes in relation to risk of developing systemic lupus erythematosus. J Rheumatol 31:76-80

Parks, Christine G; Pandey, Janardan P; Dooley, Mary Anne et al. (2004) Genetic polymorphisms in tumor necrosis factor (TNF)-alpha and TNF-beta in a population-based study of systemic lupus erythematosus: associations and interaction with the interleukin-1alpha-889 C/T polymorphism. Hum Immunol 65:622-31

Su, Kaihong; Wu, Jianming; Edberg, Jeffrey C et al. (2004) A promoter haplotype of the immunoreceptor tyrosine-based inhibitory motif-bearing FcgammaRIIb alters receptor expression and associates with autoimmunity. I. Regulatory FCGR2B polymorphisms and their association with systemic lupus erythematosus. J Immunol 172:7186-91

Parks, C G; Hudson, L L; Cooper, G S et al. (2004) CTLA-4 gene polymorphisms and systemic lupus erythematosus in a population-based study of whites and African-Americans in the southeastern United States. Lupus 13:784-91