Relevant residues of drβ1 third hypervariable region contributing to the expression and to severity of rheumatoid arthritis (ra) in mexicans

Hector Debaz, Angelica Olivo, Miriam N. Vazquez Garcia, Gabriela De La Rosa, Arturo Hernandez, Leticia Lino, Ruben Burgos, Marcelo Fernandez-Viña, Peter Stastny, Clara Gorodezky

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Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destruction of the joints. Residues at positions 67-74 of the DRB1 third hypervariable region are involved in susceptibility (S) and resistance (P) to RA. DNA from 83 patients and 175 controls, all of them Mexican Mestizos were oligotyped using PCR-SSOP and PCR-SSP. The (S) alleles are DRB1 * 0404 (p = 0.000004), *0401 (p = 0.007) and *1001 (p = 0.008). Those associated with P are DRBl * 0701 (p = 0.0001); * 1101 (p = 0.01); * 1503 (p = 0.02); * 0801 (p = 0.04); * 1401 (p = 0.04). Susceptibility/protection are recessive traits; SS genotypes are increased in the patients (p = 0.0003) while PP genotypes are decreased in them (p = 0.00004). The motif at 67-74 and the valine or glycine at position 86 are relevant in the development and severity of RA in Mexicans. The associations suggest that residues 67, 70, 71 are central for susceptibility. The P alleles have D-70 or carry V-86 in the absence of D-70. Thus, susceptibility/protection depends on the combination of basic residues at these positions and a non-polar aa at 86 contributes to resistance. Severity is also HLA influenced. DQA1 * 03011-DQB1 * 0302 are associated to severe lesions in the presence of any DR4 subtype. Analyzing different ethnic groups is essential to elucidate the etiopathogenesis of RA.

Original languageEnglish (US)
Pages (from-to)287-294
Number of pages8
JournalHuman Immunology
Volume59
Issue number5
DOIs
StatePublished - May 1 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Debaz, H., Olivo, A., Vazquez Garcia, M. N., De La Rosa, G., Hernandez, A., Lino, L., Burgos, R., Fernandez-Viña, M., Stastny, P., & Gorodezky, C. (1998). Relevant residues of drβ1 third hypervariable region contributing to the expression and to severity of rheumatoid arthritis (ra) in mexicans. Human Immunology, 59(5), 287-294. https://doi.org/10.1016/S0198-8859(98)00017-2