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Effects of Amerindian Genetic Ancestry on Clinical Variables and Therapy in Patients with Rheumatoid Arthritis
Elena Sánchez1,2, Ignacio García de la Torre1,2, Mónica Sacnún1,2
1From the Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA; Departamento de Inmunología y Reumatología, Hospital General de Occidente y Universidad de Guadalajara, Zapopan; Unidad de Investigación "Dr. Mario Alvizouri Muñoz" Hospital General "Dr. Miguel Silva," Secretaría de Salud de Michoacán, Morelia; Servicio de Reumatología del Departamento de Medicina Interna, Facultad de Medicina y Hospital Universitario "Dr. José Eleuterio González," Universidad Autonoma de Nuevo León, Monterrey; Departamento de Reumatología, Hospital General de Culiacán, Culiacán; Unidad de Reumatología, Hospital General de México "Dr. Eduardo Liceaga"; Unidad de Biología Molecular y Medicina Genómica from Instituto de Investigaciones Biomédicas de la Universidad Nacional Autónoma de México, and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; Hospital Provincial de Rosario; Instituto Lucha Antipoliomielítica de Rosario (ILAR); Hospital Escuela Eva Perón, Granadero Baigorria; Hospital José Maria Cullen; Hospital J.B. Iturraspe, Santa Fe; Hospital San Martín, Paraná; Hospital Privado de Córdoba; Hospital Italiano de Córdoba; Instituto Reumatológico Strusberg, Córdoba; Hospital Cosme Argerich; Hospital Italiano de Buenos Aires; Organización Médica Integral; Centro de Educación Médica e Investigaciones Clínicas (CEMIC); Instituto de Rehabilitación Psicofísica (IREP); Hospital Bernardino Rivadavia; Hospital de Clínicas de Buenos Aires, Buenos Aires; H.I.G.A. San Martín, La Plata; H.I.G.A. Oscar E. Alende, Mar del Plata; Centro Medico Privado de Reumatología; FUNIPSE, San Miguel de Tucumán, Tucumán; Hospital Interzonal San Juan Bautista, Catamarca; Hospital G. Rawson, San Juan; Sanatorio Parque, Rosario, Argentina; Facultad Medicina Occidente, and Facultad de Medicina Campus Centro, Universidad de Chile, Santiago de Chile, Chile; Servicio de Reumatología, Hospital Nacional Guillermo Almenara I, EsSalud y Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Perú; GENYO, Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica, Granada, Spain; Unit of Chronic Inflammatory Diseases, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Objective:
To define whether Amerindian genetic ancestry correlates with clinical and therapeutic variables in admixed individuals with rheumatoid arthritis (RA) from Latin America.
Methods:
Patients with RA (n = 1347) and healthy controls (n = 1012) from Argentina, Mexico, Chile, and Peru were included. Samples were genotyped for the Immunochip v1 using the Illumina platform. Clinical data were obtained through interviews or the clinical history.
Results:
Percentage of Amerindian ancestry was comparable between cases and controls. Morning stiffness (p < 0.0001, OR 0.05), rheumatoid factor (RF; p < 0.0001, OR 0.22), radiographic changes (p < 0.0001, OR 0.05), and higher number of criteria were associated with lower Amerindian ancestry after Bonferroni correction. Higher Amerindian ancestry correlated only with weight loss (pBonferroni < 0.0001, OR 2.85). Increased Amerindian ancestry correlated with higher doses of azathioprine (p < 0.0001, OR 163.6) and sulfasalazine (p < 0.0001, OR 48.6), and inversely with methotrexate (p = 0.001, OR 0.35), leflunomide (p = 0.001, OR 0.16), and nonsteroidal antiinflammatory drugs (pBonferroni = 0.001, OR 0.37). Only the presence of RF and weight loss were modified after confounders adjustment.
Conclusion:
Amerindian ancestry protects against most major clinical criteria of RA, but regarding the association of RF with increased European ancestry, age, sex, and smoking are modifiers. Ancestry also correlates with the therapeutic profiles.
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