- Full (HTML) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Glinda S. Cooper,¹ Frederick W. Miller,² and Janardan P. Pandey³

¹Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina USA; ²Laboratory of Molecular and Developmental Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland USA; ³Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, South Carolina USA

Abstract

Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA) , systemic lupus erythematosus (SLE) , type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci ; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases. Key words: autoimmune diseases, gene-environment interactions, genetics, major histocompatibility complex, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes mellitus. -- Environ Health Perspect 107(suppl 5) :693-700 (1999) .

http://ehpnet1.niehs.nih.gov/docs/1999/suppl-5/693-700cooper/abstract.html