Genetic marker research and the tribal records of Oklahoma's Choctaw indians have come together to help track the connective tissue disease scleroderma in its mercilous march through the Choctaws.

The research, coordinated by the National Institute of Arthritis and Musculoskeletal and Skin Disease Specialized Center of Research in Scleroderma at the University of Texas-Houston Health Science Center, identified a chromosomal site associated with scleroderma. The study implicated the gene for the protein fibrillin-1 as a possible susceptibility gene for the disease, which is characterized by tissue scarring within skin, internal organs, and small blood vessels. Fibrillin-1 also has been found responsible for a scleroderma-like condition in a mouse model of the human disease.

Working with 18 Choctaw scleroderma patients and 77 healthy Choctaw subjects, scientists analyzed sites on human chromosomes 15q and 2q that corresponded to locations identified in the scleroderma mouse models. At the same time, the scientists examined census and other Choctaw patient records dating back to the 1800s.

The studies showed a specific DNA sequence on chromosome 15q that occurred with a frequency significantly higher in Choctaw patients with scleroderma than in Choctaws without it. The sequence also contained genetic markers for the fibrillin-1 gene. At the same time, the genealogical evidence showed that the Choctaw scleroderma cases could be traced to five families in the mid-18th century. The sequence may have been inherited from common disease founders about 10 generations ago. The findings are specific to descendants of five Choctaw families that were studied, making the greater incidence of scleroderma among Choctaws a familial rather than ethnic phenomenon.

The study moves scleroderma research a step closer to identifying a susceptibility gene. The autoimmune disorder occurs more frequently in women than in men, usually between the ages of 45 and 55. The hallmark of scleroderma is widespread thickening of the skin. The scleroderma in this study, systemic sclerosis, also involves fibrosis or scarring of tissues in the lungs, heart, kidneys, intestinal tract, muscles, and joints. Although its cause is unknown, researchers believe that other environmental and genetic factors may play a role in scleroderma.

— Lee Landenberger