title: HLA-DRB1 alleles encoding the "shared epitope" are associated with susceptibility to developing rheumatoid arthritis whereas HLA-DRB1 alleles encoding an aspartic acid at position 70 of the beta-chain are protective in Mexican Mestizos.
abstract: The risk to develop rheumatoid arthritis (RA) has been associated with the presence of HLA-DRB1 alleles encoding the "shared epitope" (SE). Additionally, HLA-DRB1 alleles encoding an aspartic acid at position 70 (D70+ ) have been associated with protection against the development of RA. In this study we tested the association between either SE or D70+ and rheumatoid arthritis in Mexican Mestizos. We included 84 unrelated Mexican Mestizos patients with RA and 99 unrelated healthy controls. The HLA-typing was performed by PCR-SSO and PCR-SSP. We used the chi-squared test to detect differences in proportions of individuals carrying at least one SE or D70+ between patients and controls. We found that the proportion of individuals carrying at least one HLA-DRB1 allele encoding the SE was significantly increased in RA cases as compared to controls (p(c) = 0.0004, OR = 4.1, 95% CI = 2.2-7.7). The most frequently occurring allele was HLA-DRB1*0404 (0.161 vs 0.045). Moreover, we observed a significantly increased proportion of HLA-DRB1 SE+ cases with RF titers above the median (p = 0.005). Conversely, the proportion of individuals carrying at least one HLA-DRB1 allele encoding the D70+ was significantly decreased (p(c) = 0.004, OR = 0.4, 95% CI 0.2-0.7) among RA patients compared with controls. In conclusion, the SE is associated with RA in Mexican Mestizos as well as with the highest titers of RF.
authors.affiliation: Department of Immunology and Rheumatology (J.A.R.-M., C.V.-G., J.K.Y.-F., M.R., M.H.C., J.G.), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico.
authors.forename: J A
authors.initials: JA
authors.lastname: Ruiz-Morales
authors.forename: G
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.forename: P O
authors.initials: PO
authors.lastname: Flores-Villanueva
authors.forename: C
authors.initials: C
authors.lastname: Villarreal-Garza
authors.forename: G
authors.initials: G
authors.lastname: Hernández-Pacheco
authors.forename: J K
authors.initials: JK
authors.lastname: Yamamoto-Furusho
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez-Pérez
authors.forename: N
authors.initials: N
authors.lastname: Pérez-Hernández
authors.forename: M
authors.initials: M
authors.lastname: Rull
authors.forename: M H
authors.initials: MH
authors.lastname: Cardiel
authors.forename: J
authors.initials: J
authors.lastname: Granados
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001224:Aspartic Acid / Q000235:genetics; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D001224:Aspartic Acid