HLA-DRB1 alleles associated with susceptibility or resistance to rheumatoid arthritis, articular deformities, and disability in Mexican Americans

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Abstract
Objective To study the genetics (HLA–DRB1 allele associations) of rheumatoid arthritis (RA) susceptibility and severity among Mexican Americans, an important, but understudied, US population. Methods HLA–DRB1 alleles were compared between 141 Mexican American patients with RA and 54 unrelated Mexican Americans without RA, and the association of these alleles with articular deformities and disability was examined. HLA–DRB1 alleles were typed using polymerase chain reaction–sequence-specific primer amplification and were classified according to the 1996 World Health Organization nomenclature. Results Of the 141 patients, 105 (74%) had at least 1 copy of the shared epitope (SE) sequence, compared with 29 (54%) of the 54 controls (P = 0.007). A significant gene-dose effect was observed, with 31 patients (22%) being homozygous for the SE compared with 1 (2%) of the controls (P = 0.004). In terms of disease severity, only 3% of RA patients who were “null” for the SE were outliers in the rate of development of articular deformities, compared with 10% of heterozygotes and 27% of homozygotes (P = 0.002). Patients who were DRB1*08 positive had significantly fewer deformities per year of disease and a slower rate of development of disability than did patients with other DRB1 alleles. Conclusion HLA–DRB1 alleles containing the SE are associated with susceptibility to RA in Mexican Americans, and may also be associated with a more rapid development of articular deformities and disability. HLA–DRB1*08 appears to have a protective influence on RA susceptibility and disease severity in Mexican Americans.