Статья

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

David López HerráezCentro Pfizer–Universidad de Granada–Junta de Andalucía de Genómica e Investigaciones Oncológicas, Granada, SpainManuel Martínez‐BuenoCentro Pfizer–Universidad de Granada–Junta de Andalucía de Genómica e Investigaciones Oncológicas, Granada, SpainLaura RibaInstituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoIgnacio García‐De La TorreHospital General de Occidente and Universidad de Guadalajara, Zapopan, MexicoM. SacnúnHospital Provincial de Rosario, Rosario, ArgentinaMario GoñiGuillermo BerbottoSergio PairaJorge L. MusuruanaCésar GrafAlejandro AlvarellosHospital Privado de Córdoba, Córdoba, ArgentinaOsvaldo Daniel MessinaHospital Cosme Argerich, Buenos Aires, ArgentinaAlejandra BabiniHospital Italiano de Córdoba, Córdoba, ArgentinaIngrid StrusbergInstituto Reumatológico Strusberg, Córdoba, ArgentinaJuan Carlos MarcosCentro Pfizer–Universidad de Granada–Junta de Andalucía de Genómica e Investigaciones Oncológicas, Granada, SpainHugo R. ScherbarthHospital Interzonal General de Agudos Oscar E. Alende, Mar del Plata, ArgentinaAlberto SpindlerCentro Medico Privado de Reumatología, San Miguel de Tucumán, ArgentinaA. QuinterosSergio TolozaJosé Luis C. MorenoLuís J. CatoggioHospital Italiano de Buenos Aires, Buenos Aires, ArgentinaGuillermo TateAlicia EimonCentro de Educación Médica e Investigaciones Clínicas, Buenos Aires, ArgentinaGustavo CiteraInstituto de Rehabilitación Psicofísica, Ciudad Autónoma de Buenos Aires, ArgentinaAntonio Catalán PelletHospital Bernardino Rivadavia, Ciudad Autónoma de Buenos Aires, ArgentinaGustavo NasswetterHospital de Clínicas de Buenos Aires, Buenos Aires, ArgentinaMario H. CardielUnidad de Investigación “Dr. Mario Alvizouri Muñoz,” Hospital General “Dr. Miguel Silva,” Secretaría de Salud de Michoacán, Morelia, Michoacán, MexicoPedro C. MirandaUniversidad de Chile, Santiago de Chile, ChileFrancisco J. BallesterosUniversidad de Chile, Santiago de Chile, ChileJorge Antonio Esquivel‐ValerioHospital Universitario Dr. José Eleuterio González and Universidad Autonoma de Nuevo León, Monterrey, MexicoMarco A. Maradiaga‐CeceñaHospital General de Culiacán, Culiacán, MexicoEduardo M. Acevedo‐VásquezHospital Nacional Guillermo Almenara Irigoyen EsSalud and Universidad Nacional Mayor de San Marcos, Lima, PeruConrado García-GarcíaHospital General de México Dr. Eduardo Liceaga, Mexico City, MexicoTeresa Tusié‐LunaInstituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, MexicoBernardo A. Pons‐EstelSanatorio Parque, Rosario, ArgentinaMarta E. Alarcón‐RiquelmeCentro Pfizer–Universidad de Granada–Junta de Andalucía de Genómica e Investigaciones Oncológicas, Granada, Spain, and Oklahoma Medical Research Foundation, Oklahoma City

2013en

ABI

Аннотация

OBJECTIVE: To identify susceptibility loci for rheumatoid arthritis (RA) in Latin American individuals with admixed European and Amerindian genetic ancestry. METHODS: Genotyping was performed in 1,475 patients with RA and 1,213 control subjects, using a customized BeadArray containing 196,524 markers covering loci previously associated with various autoimmune diseases. Principal components analysis (EigenSoft package) and Structure software were used to identify outliers and define the population substructure. REAP software was used to define cryptic relatedness and duplicates, and genetic association analyses were conducted using Plink statistical software. 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(-10) ), with 3 independent effects. We identified an association in the PLCH2-HES5-TNFRSF14-MMEL1 region of chromosome 1 (P = 9.77 × 10(-6) ), 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(-7) ). 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(-6) ). 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.

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Идентификаторы

DOI: 10.1002/art.37923

Цитирования и источники

Цитирований: 2Использованных источников: 0

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