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

Objective. To study the genetics (HLA-DRB1 allele associations) of rheumato id arthritis (RA) susceptibility and severity among Mexican Americans, an i mportant, but understudied, US population. Methods. HLA-DRB1 alleles were compared between 141 Mexican American patien ts with RA and 54 unrelated Mexican Americans without RA, and the associati on of these alleles with articular deformities and disability was examined. HLA-DRB1 alleles were typed using polymerase chain reaction-sequence-speci fic primer amplification and were classified according to the 1996 World He alth Organization nomen-clature. Results. Of the 141 patients, 105 (74%) had at least 1 copy of the shared e pitope (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, compa red with 10% of heterozygotes and 27% of homozygotes (P = 0.002), Patients who were DRB1*08 positive had significantly fe,ver deformities per year of disease and a slower rate of development of disability than did patients wi th other DRB1 alleles. Conclusion, HLA-DRB1 alleles containing the SE are associated with suscepti bility to RA in Mexican Americans, and may also be associated with a more r apid development of articular deformities and disability. HLA-DRB1*08 appea rs to have a protective influence on RA susceptibility and disease severity in Mexican Americans.