(Arthritis and Rheumatism) -- Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by changes in the skin--thickening, hardness, discoloration, ulcerations--as well as joint stiffness, swelling of fingers, and sensitivity to the cold. In addition to being painful and sometimes disfiguring, SSc can cause damage to small blood vessels within the skin and internal organs. Researchers have suspected genetic factors play a role occurs recurs infrequently in families, genetic linkage studies of SSc have proven difficult.

Recently, a team of researchers specializing in musculoskeletal and skin disorders identified a unique population: a community of Oklahoma Choctaw Indians with a high prevalence of SSc. Led by Dr. Frank C. Arnett of the University of Texas-Houston Medical School, and supported by grants from the National Institutes of Health, the team used this unique opportunity to search for a genetic predisposition to this autoimmune disease. The results of their study, published in the September 2003 issue of Arthritis & Rheumatism, shed light on the role of genes in not only SSc but other rheumatic diseases associated with disturbed immune function.

For every 100,000 Caucasians, SSc affects less than 25. For every 100,000 Choctaws, SSc affects nearly 500. Most of the SSc cases in the Oklahoma Choctaw population have been traced to a common founding family in the mid-1700s. On the strength of this evidence, Dr. Arnett and his team set out to map the genomes of Choctaw patients. Of the Choctaw population, they screened 20 SSc patients for common genetic markers and compared the results with healthy Choctaw controls. Except for one pair of SSc cases--first cousins-- the patterns of heredity among the Choctaws with the disease were not discernibly different from those among those spared.

As a result of their targeted genetic survey, researchers found a total of 17 candidate genetic regions that may contribute to SSc susceptibility. Strikingly, some of the potential genetic determinants of SSc have also been linked to systemic lupus erythematosus (SLE), commonly known as lupus; ankylosing spondylitis, an inflammatory disease of the spine; and insulin-dependent diabetes.

"It appears likely that SSc-specific genetic determinants along with genes shared with other autoimmune diseases play combinational roles in the development of SSc," contends Dr. Xiaodong Zhou, a member of the team. "With the human genome now sequenced and available, these candidate regions need to be examined more closely to identify the actual predisposing genes. Such studies are in progress."