INCREASED PREVALENCE OF SYSTEMIC-SCLEROSIS IN A NATIVE-AMERICAN TRIBEIN OKLAHOMA - ASSOCIATION WITH AN AMERINDIAN HLA HAPLOTYPE

Objective. To investigate a high prevalence of systemic sclerosis (SSc ; scleroderma) in a well-defined population of 21,255 Choctaw Indians residing in 8 southeastern Oklahoma counties who were ''users'' of Ind ian Health Services, Methods. A case-control study of 12 SSc cases and 48 matched non-SSc controls (4 per case) was conducted to investigate potential occupational, residential, and infectious exposures, as wel l as genetic factors which might predispose to SSc, HLA class II allel es were determined by DNA oligotyping, and class I and III alleles wer e defined serologically. Results, The prevalence of SSc in full-bloode d Choctaws was at least 8/1,704, or 469/100,000 (95% confidence interv al [95% CI] 203-930) over the 4-year interval 1990-1994 and was signif icantly higher than that among non-full-blooded Choctaws (6/19,551, or 31/100,000) (P = 0.00001, odds ratio [OR] = 15.4, 95% CP 4.9-49.8), T he overall prevalence of SSc in Oklahoma Choctaws (66/100,000) also wa s significantly higher than that in other Native Americans in Oklahoma (9.5/100,000) (P = 10(-6), OR = 6.95, 95% CI 3.3-13.7), who showed a prevalence similar to that reported for whites (2.1-25.3/100,000). Amo ng the SSc cases, there was striking homogeneity of disease expression with the majority exhibiting diffuse scleroderma, pulmonary fibrosis, and autoantibodies to topoisomerase I, No environmental exposures wer e found to be in excess among cases versus controls, The strongest ris k factor for SSc in cases (100%) versus controls (54%) was an HLA hapl otype bearing the alleles B35, Cw4, DRB11602 (DR2), DQA1*0501, and DQ B10301 (DQ7) (P = 0.002, P-corr = 0.036, OR = 21, 95% CI 2.9-437), Su rvey of another group of Choctaws residing in another state revealed n o cases of SSc despite a high frequency of the same BLA haplotype, Con clusion, Full-blooded Choctaw Native Americans living in southeastern Oklahoma have the highest prevalence of SSc yet found in any populatio n, A major risk factor for disease is a uniquely Amerindian HLA haplot ype; however, additional genes and/or an as-yet-unidentified environme ntal exposure seem likely.