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Polymorphisms in the IL4 and IL4RA Genes in Colombian Patients with Rheumatoid Arthritis
OLGA MORENO, CLARA ISABEL GONZÁLEZ, DIEGO LUIS SAAIBI, WILLIAM OTERO, REYNALDO BADILLO, JAVIER MARTÍN, and GERARDO RAMÍREZ ABSTRACT. Objective. Rheumatoid arthritis (RA) is considered a Th1-driven disease. Interleukin 4 (IL-4) binds to its receptor, promoting Th2 differentiation and limiting Th1 responses, but its role in the pathogenesis of RA is conflicting. We analyzed 2 polymorphisms of the IL4 gene and 4 polymorphisms of the IL4RA gene in patients with RA and in a control population, as well as rheumatoid factor (RF) seropositivity, titers of RF, and history of replacement joint surgery among patients with RA. Methods. The study population consisted of 102 patients with RA and 102 matched healthy controls. Genotyping of IL4 –590, IL4RA +148, +1124, +1218, and +1902 was determined by restriction fragment length polymorphism-polymerase chain reaction (PCR) and sequence-specific primer-PCR. IL4 variable number tandem repeat polymorphism was determined by direct amplification. Results. The IL4 –590TT genotype was significantly more frequent in patients with RA than in controls (p = 0.018, OR 3.34, 95% CI 1.08–11.04). The IL4RA +148A allele was significantly associated with the presence of RF (p = 0.0019, OR 2.55, 95% CI 1.55–4.86) and a history of articular joint replacement (p = 0.024, OR 2.08, 95% CI 1.04–4.18). The IL4RA +1902G allele was more frequently seen in patients with RA and high RF titers (p = 0.00067, OR 4, 95% CI 1.64–9.93). Conclusion. Highly complex pathways lead to the development of RA and may not be similar in all patients. Our findings of higher frequency of IL4 and IL4RA genotypes and alleles with RA, presence of RF, RF titers, and history of articular joint replacement support the polygenic expression of RA and the likely role of IL-4 in influencing its initiation and development. (First Release Dec 1 2006; J Rheumatol 2007;34:36–42) Key Indexing Terms:
RHEUMATOID ARTHRITIS From the Laboratorio de Inmunología y Biología Molecular, Grupo de Inmunología y Epidemiología Molecular, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga; Clínica Carlos Ardila Lulle, Floridablanca, Santander; and Departamento de Medicina Interna, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia; and the Instituto de Parasitología y Biomedicina López-Neyra, Granada, Spain. Supported by grant 1102-04-12905 from Colciencias and Universidad Industrial de Santander. O. Moreno, MSc; C.I. González, PhD, Laboratorio de Inmunología y Biología Molecular, Grupo de Inmunología y Epidemiología Molecular, Facultad de Salud, Universidad Industrial de Santander; D.L. Saaibi, MD, Clínica Carlos Ardila Lulle; W. Otero, MD; R. Badillo, MD, Departamento de Medicina Interna, Facultad de Salud, Universidad Industrial de Santander; J. Martin, MD, PhD, Instituto de Parasitología y Biomedicina López-Neyra; G. Ramírez, MD, Laboratorio de Inmunología y Biología Molecular, Grupo de Inmunología y Epidemiología Molecular, Facultad de Salud, Universidad Industrial de Santander, Clínica Carlos Ardila Lulle. Address reprint requests to Dr. G. Ramírez, Laboratorio de Inmunología y Biología Molecular, Facultad de Salud, Carrera 32 # 29-31, Universidad Industrial de Santander, Bucaramanga, Colombia AA 678. E-mail: gemensu@yahoo.com Accepted for publication September 20, 2006. |
