학술논문
Rheumatoid Arthritis in Latin Americans Enriched for Amerindian Ancestry is Associated With Loci in Chromosomes 1, 12, and 13, and the HLA Class II Region
Document Type
Academic Journal
Author
Herráez, David López; Martínez-Bueno, Manuel; Riba, Laura; de la Torre, Ignacio García; Sacnún, Mónica; Goñi, Mario; Berbotto, Guillermo A.; Paira, Sergio; Musuruana, Jorge Luis; Graf, César E.; Alvarellos, Alejandro J.; Messina, Osvaldo D.; Babini, Alejandra M.; Strusberg, Ingrid; Marcos, Juan Carlos; Scherbarth, Hugo; Spindler, Alberto J.; Quinteros, Ana; Toloza, Sergio M. A.; Moreno, José Luis C.; Catoggio, Luis J.; Tate, Guillermo; Eimon, Alicia; Citera, Gustavo; Catalán Pellet, Antonio; Nasswetter, Gustavo G.; Cardiel, Mario H.; Miranda, Pedro; Ballesteros, Francisco; Esquivel-Valerio, Jorge A.; Maradiaga-Ceceña, Marco A.; Acevedo-Vásquez, Eduardo M.; García García, Conrado; Pons-Estel, Bernardo A.; Alarcón-Riquelme, Marta E.
Source
Arthritis & Rheumatism. Jun 01, 2013 65(6):1457-1467
Subject
Language
English
ISSN
0004-3591
Abstract
OBJECTIVE: METHODS: RESULTS: A strong genetic association between RA and the major histocompatibility complex region was observed, localized within BTNL2/DRA–DQB1– DQA2 (P = 7.6 × 10), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10), which was previously reported in Europeans, Asians, and Native Canadians. We identified one novel putative association in ENOX1 on chromosome 13 (P = 3.24 × 10). Previously reported associations were observed in the current study, including PTPN22, SPRED2, STAT4, IRF5, CCL21, and IL2RA, although the significance was relatively moderate. Adjustment for Amerindian ancestry improved the association of a novel locus in chromosome 12 at C12orf30 (NAA25) (P = 3.9 × 10). Associations with the HLA region, SPRED2, and PTPN22 improved in individuals positive for anti–cyclic citrullinated peptide antibodies. CONCLUSION: Our data define, for the first time, the contribution of Amerindian ancestry to the genetic architecture of RA in an admixed Latin American population by confirming the role of the HLA region and supporting the association with a locus in chromosome 1. In addition, we provide data for novel putative loci in chromosomes 12 and 13.