Frequency of human leukocyte antigens class II-DR alleles (HLA-DRB1) in Argentinian patients with early arthritis
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Patients with rheumatoid arthritis (RA) or undifferentiated arthritis (UA) in the CONAART database (Argentine Consortium for Early Arthritis) were assessed for genetic risk factors for RA, specifically for HLA-DRB1 alleles and the PTPN22 rs2476601 polymorphism associated with progression to RA. This is a case-control study. Blood samples were obtained to determine HLA-DRB1 genotypes by PCR-SSO Luminex and PTPN22 (rs2476601) polymorphism by allelic discrimination. A control group of individuals from the general Argentinian population were obtained from the national register of cadaveric organ donors. A total of 1859 individuals were included in this analysis: 399 patients from the CONAART database (347 patients with RA at study end and 52 patients with UA at study end, mean follow-up time 25 ± 18 months) and 1460 individuals from the general Argentinian population. Compared with the controls, the HLA-DRB1*04 and DRB1*09 alleles were more commonly detected in patients with RA diagnosis (OR (95% CI) 2.23 (1.74–2.85) and 1.89 (1.26–2.81)) respectively. Both patients with UA and the general population showed higher frequency of DRB1*07, DRB1*11 and DRB1*15 alleles than patients with RA. PTPN22 rs2476601 polymorphism frequency was higher in RA and UA vs the general population; however, this was significantly different only for RA vs control group (OR [95% CI] = 1.81 [1.10–3.02], P = 0.018. HLA-DRB1 typing and PTPN22 allelic discrimination could distinguish between patients with UA, patients with early RA, and the general population in Argentina. This is the first study of HLA-DRB1 alleles and PTPN22 polymorphism associations with progression to early RA in an Argentinian population.
KeywordsEarly arthritis Genetics Rheumatoid arthritis Shared epitope Undifferentiated arthritis
The authors wish to thank all patients who participated in this study; they also wish to thank all the colleagues who during their fellowship participated in the evaluation of patients in CONAART (Margarita Landi MD, Alejandro Cayetti MD, Ana Lizarraga MD, Federico Ceccato MD).
The work was sponsored by an unrestricted grant from Pfizer Argentina. Pfizer had interference neither in driving nor in the analysis or writing of the study.
Compliance with ethical standards
- 8.Begovich AB, Carlton VE, Honigberg LA, Schrodi SJ, Chokkalingam AP, Alexander HC et al (2004) A missense single-nucleotide polymorphism in a gene encoding a protein tyrosine phosphatase (PTPN22) is associated with rheumatoid arthritis. Am J Hum Genet 75(2):330–337CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Barros Bértolo M, Lavras Costallat LT, Persoli LB, Ferreira CF (2001) HLA-DRB1 alleles and the prognosis of rheumatoid arthritis in Brazilian patients. Rev Bras Reumatol 41:151–156Google Scholar
- 14.Ruiz-Morales JA, Vargas-Alarcon G, Flores-Villanueva PO, Villarreal-Garza C, Hernandez-Pacheco G, Yamamoto-Furusho JK et al (2004) 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. Hum Immunol 65(3):262–269CrossRefPubMedGoogle Scholar
- 15.Debaz H, Olivo A, Vazquez Garcia MN, de la Rosa G, Hernandez A, Lino L, Burgos R, Fernandez-Viña M, Stastny P, Gorodezky C (1998) Relevant residues of DRbeta1 third hypervariable region contributing to the expression and to severity of rheumatoid arthritis (RA) in Mexicans. Hum Immunol 59(5):287–294CrossRefPubMedGoogle Scholar
- 18.Angulo J, Miraval T, Ponce de León H, Reveille J (2003) Epítope reumatoide y alelo HLA-DRB1⁎0404 se asocian con susceptibilidad para artritis reumatoide en mestizos peruanos. Rev Peru Reumatol 9:26–32Google Scholar
- 20.Torres-Carrillo NM, Ruiz-Noa Y, Martinez-Bonilla GE, Leyva-Torres SD, Torres-Carrillo N, Palafox-Sanchez CA et al (2012) The +1858C/T PTPN22 gene polymorphism confers genetic susceptibility to rheumatoid arthritis in Mexican population from the Western Mexico. Immunol Lett 147(1–2):41–46CrossRefPubMedGoogle Scholar
- 23.Marcos J, Waimann C, Dal Pra F, Hogrefe J, Retamozo S, Caeiro F, Casalla L, Benegas M, Rillo O, Spindler A, Berman H, Berman A, Secco A, Garcia Salinas R, Catalan Pellet A, Ceccato F, Paira S, Marcos JC, Maldonado Cocco JA, Citera G, on behalf of CONAART (Consorcio Argentino de Artritis Temprana—Argentine Consortium for Early Arthritis) (2011) General characteristics of an early arthritis cohort in Argentina. Rheumatology (Oxford) 50(1):110–116CrossRefGoogle Scholar
- 27.van der Heijde DM, van Riel PL, van Leeuwen MA, van’t Hof MA, van Rijswijk MH, van de Putte LB (1992) Prognostic factors for radiographic damage and physical disability in early rheumatoid arthritis. A prospective follow-up study of 147 patients. Br J Rheumatol 31(8):519–525CrossRefPubMedGoogle Scholar