METAANALYSIS REVEALS ASSOCIATION BETWEEN MOST COMMON CLASS-II HAPLOTYPE IN FULL-HERITAGE NATIVE-AMERICANS AND RHEUMATOID-ARTHRITIS

The association of RA with the alleles at the HLA system was tested am ong Pima and Tohono O'odham Indians (Pimans) of the Gila River Indian Community of Arizona. Serologic class I (HLA-A, -B, and -C) alleles we re typed in 51 individuals with RA and in 302 without RA. Serologic cl ass II (HLA-DR, DQ; DR52 DR53) alleles were typed in a subset of 47 wi th RA and 147 without RA. Molecular subtypes of DR3Xb, DRB1()1402, an d ()1406 were determined in 29 individuals, 16 with RA and 13 without RA. Among the cases with RA, 46 of 47 had the serologic antigen HLA-D R3X6, as did 140 of 147 of those without the disease. However, this as sociation was not statistically significant because of the high preval ence of the antigen in the controls. Data from Pimans were analyzed wi th similar results from the Tlingit and Yakima Indians. A meta-analysi s employing the Mantel-Haenszel procedure, stratified by tribe, reveal ed a statistically significant association between the most common hap lotype, DRB1()1402 DQA1(*)0501 DQB1(*)0301 DRB3(*)0101, and RA (summa ry odds ratio = 2.63, 95% confidence interval = 1.08, 6.46). There was also a statistically significant difference in the genotype distribut ions of one class I locus, HLA-C, between those with and without RA(ch i(2) = 12.4, 5 df, p = 0.03). It is concluded that the association wit h the most common class II haplotype in full-heritage Native Americans might help explain their high prevalence of RA.