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The role of HLA-DR alleles and complotypes through the ethnic barrier in systemic lupus erythematosus in Mexicans

Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City

G. Vargas-Alarcón

Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City

F. Andrade

Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City

H. Melin-Aldana

Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City

J. Alcocer-Varela

Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City

D. Alarcón-Segovia

Department of Immunology and Rheumatology, Instituto Nacional de la Nutrición Salvador Zubirán, Mexico City

Alleles of the major histocompatibility complex (MHC) have been recognized as genetic factors for the development of SLE. The [HLA-B8; SC01; DR3] extended haplotype seems to be relevant in patients from white European descent, pertinent alleles, however, are diffi cult to select on haplotypes with linkage disequilibrium. Studies in non-Caucasian patients are therefore mandatory. Admixture estimates in Mexicans have shown a proportion of 56% of Indian genes, 40% of Caucasian genes and from 4 to 12% of Black genes. In order to determine the relevant MHC loci 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 relatives and compared these two groups to another one composed by 200 ethnically 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, first degree relatives had a significantly increased frequency of HLA-DR7 (pC = 0.01, RR = 2.98). There were 21 out of 33 HLA-DR3 haplotypes with complotypes other than SC01 and 25 out 37 SC01 haplotypes with DR alleles other than DR3. Neverthe less, [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 increased (p = 0.04, RR = 2.1). We also found in SLE patients significantly decreased fre quencies of the autochthonous Mexican alleles (A30, B39 and 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 predisposition to SLE in Mexican patients which might be high tened by genes located around the class III MHC region. They also substantiate the perti nence of ethnic admixture estimates in modern human populations.

Key Words: systemic lupus erythematosus • major histocompatibility complex (MHC) • MHC haplotypes • susceptibility

Lupus, Vol. 5, No. 3, 184-189 (1996)
DOI: 10.1177/096120339600500304


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