THE ROLE OF HLA-DR ALLELES AND COMPLOTYPES THROUGH THE ETHNIC BARRIERIN SYSTEMIC LUPUS-ERYTHEMATOSUS IN MEXICANS

Alleles of the major histocompatibility complex (MHC) have been recogn ized as genetic factors for the development of SLE. The [HLA-B8; SC01; DR3] extended haplotype seems to be relevant in patients from white E uropean descent, pertinent alleles, however, are difficult to select o n haplotypes with linkage disequilibrium. Studies in non-Caucasian pat ients are therefore mandatory. Admixture estimates in Mexicans have sh own a proportion of 56% of Indian genes, 40% of Caucasian genes and fr om 4 to 12% of Black genes. In order to determine the relevant MHC loc i in the genetic susceptibility for SLE we studied Class I, II and III alleles in 102 Mexican SLE patients and 350 of their first degree rel atives and compared these two groups to another one composed by 200 et hnically matched normal individuals. We found significantly increased frequencies of HLA-DR3 (pC = 0.03, RR = 2.56) and DR7 (pC = 0.004, RR = 3.08) in SLE patients as compared to controls. On the other hand, fi rst degree relatives had a significantly increased frequency of HLA-DR 7 (pC = 0.01, RR = 2.98). There were 21 out of 33 HLA-DR3 haplotypes w ith complotypes other than SC01 and 25 out 37 SC01 haplotypes with DR alleles other than DR3. Nevertheless, [SC01; DR3] haplotypes were also increased (pC = 0.01, RR = 12.4). After removing [HLA-B8; SC01; DR3] haplotypes, DR3 was the only allele that remained significantly increa sed (p = 0.04, RR = 2.1). We also found in SLE patients significantly decreased frequencies of the autochthonous Mexican alleles (A30, B39 a nd DR4) and no deviation from normality of any of the HLA-DQ alleles. These data suggest a fundamental role of the HLA-DR3 allele in the pre disposition to SLE in Mexican patients which might be hightened by gen es located around the class III MHC region. They also substantiate the pertinence of ethnic admixture estimates in modern human populations.