RESUMO
The majority of autoimmune diseases predominate in females. In searching for an explanation for this female excess, most attention has focused on hormonal changes--both exogenous changes (for example, oral contraceptive pill) and fluctuations in endogenous hormone levels particularly related to menstruation and pregnancy history. Other reasons include genetic differences, both direct (influence of genes on sex chromosomes) and indirect (such as microchimerism), as well as gender differences in lifestyle factors. These will all be reviewed, focusing on the major autoimmune connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus and scleroderma.
Assuntos
Doenças Autoimunes/genética , Doenças Autoimunes/metabolismo , Predisposição Genética para Doença , Doenças Reumáticas/genética , Doenças Reumáticas/metabolismo , Feminino , Hormônios Esteroides Gonadais/metabolismo , Humanos , Gravidez/imunologia , Fatores de Risco , Fatores SexuaisRESUMO
This article will review how epidemiological studies have advanced our knowledge of both genetic and environmental risk factors for rheumatic diseases over the past decade. The major rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, osteoarthritis, gout, and fibromyalgia, and chronic widespread pain, will be covered. Advances discussed will include how a number of large prospective studies have improved our knowledge of risk factors, including diet, obesity, hormones, and smoking. The change from small-scale association studies to genome-wide association studies using gene chips to reveal new genetic risk factors will also be reviewed.
Assuntos
Doenças Reumáticas/epidemiologia , Doenças Reumáticas/etiologia , Animais , Meio Ambiente , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/etiologia , Predisposição Genética para Doença/genética , Humanos , Doenças Reumáticas/genética , Fatores de RiscoRESUMO
PURPOSE OF REVIEW: This review aims to summarize articles published between October 2004 and November 2005 that have investigated the genetic epidemiology of rheumatoid arthritis. RECENT FINDINGS: The consistent replication of an association between the R620W single nucleotide polymorphism in PTPN22 and rheumatoid arthritis clearly establishes this polymorphism as an important risk factor for rheumatoid arthritis. SUMMARY: Genetic investigations of rheumatoid arthritis have predominantly been single nucleotide polymorphism-based candidate gene association studies searching for markers of susceptibility, severity or treatment response. Studies of the human leukocyte antigen region have refined and added to our understanding of the complex associations to polymorphisms with this locus. PTPN22 has emerged strongly as a genuine rheumatoid arthritis susceptibility gene with replications of the association to the R620W single nucleotide polymorphism. Many investigations have been conducted on the genetics of treatment response -- some 'generic' and others specific in terms of identifying genetic influences to the mode of action and metabolism of particular agents.
