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Genes Do Contribute To Disease Susceptibility And Severity.(Brief Article)
2001 DEC 13 - (NewsRx.com & NewsRx.net) -- by Michelle Marble, senior medical writer - "Rheumatoid arthritis (RA) leads to progressive joint destruction and loss of function in some, but not all patients," said Diane Lacaille, MD, MPH, FRCPC, University of British Columbia, Arthritis Research Center of Canada. "Patients with aggressive disease have joint destruction as early as one year into their diagnosis. Identification of people at greater risk of severe disease would be helpful in guiding therapy in early RA."
Lacaille spoke at the 65th Annual Scientific Meeting of the American College of Rheumatology, held November 10-15, 2001, in San Francisco, California. Current clinical predictions are imprecise, she continued. Poor prognostic factors for aggressive disease include gender, men generally have more aggressive disease than women although women are two to three times more likely to have RA; younger age at onset; lower education; positive rheumatoid factor (RF) and higher titer; more active disease at presentation; a persistent course of disease rather than intermittent; and extra-articular manifestations of disease.
It has been shown that there is a familiar aggregation for risk of developing RA. There is an increased risk if the patient has a first degree relative, if there is a female relative of a female patient, if the relative has severe disease, and between monozygotic twins (15-30%. concordance rate, four times greater than in dizygotic twins.
Genetics account for about 60% of susceptibility. The question is which genes are responsible? According to Lacaille, the strongest associations are with major histocompatibility complex (MHC) genes, x chromosomes, RA-associated HLA alleles. MHC class II alleles are called shared epitopes, these include HLA-DRB1*0101, 0102, HLA-DRB1*0401, 0404, 0405, 0408.
"The association between HLA alleles (shared epitopes) and disease susceptibility has been established for most ethnic groups," stated Lacaille. "Shared epitopes are associated with worse prognosis in most, but not all studies. They are most frequently found in patients with more severe disease. Association has been linked to greater likelihood of positive RF, greater likelihood of extra-articular manifestations; increased rate of ...
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Source: HighBeam Research, Genes Do Contribute To Disease Susceptibility And Severity.(Brief...