title: STAT4 rs7574865 G/T polymorphism is associated with rheumatoid arthritis and disease activity, but not with anti-CCP antibody levels in a Mexican population.
abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease in whose etiology genetic factors are known to play an important role. Among the genes associated with RA, STAT4 could be an important factor in conducting helper T cells toward the pro-inflammatory Th1 and Th17 lineages. The aim of this study is to determine the association of the STAT4 polymorphism rs7574865 with RA, disease activity, and anti-cyclic citrullinated peptide (CCP) antibody levels in a Mexican population. Genotyping was carried out using the Taqman® system from Applied Biosystems in 140 patients with RA and 150 healthy subjects. Disease activity was evaluated by a rheumatologist using the DAS28 and Spanish-HAQ-DI instruments. Anti-CCP levels were determined by ELISA. Associations of the genotypes of rs7574865 with DAS28, HAQ, and anti-CCP antibody levels with RA were determined. Findings showed that the GT and TT genotypes and the T allele from rs7574865 were all associated as risk factors for RA, independently of their anti-CCP status. An association with moderate-to-high disease activity (DAS28 ≥ 3.2) was also found. Additionally, patients with the GT or TT genotypes showed lower HAQ values than those who carried the GG genotype. No differences in anti-CCP antibody levels or DAS28 and genotypes were found. This work supports the association of the STAT4 rs7574865 polymorphism with RA and disease activity, but not with anti-CCP antibody levels in a Mexican population.
authors.affiliation: Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas-Universidad Autónoma de Nayarit, Cd. de la Cultura, Amado Nervo s/n, CP 63190, Tepic, Nayarit, Mexico.
authors.forename: Ma de Jesús
authors.initials: MJ
authors.lastname: Durán-Avelar
authors.affiliation: Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas-Universidad Autónoma de Nayarit, Cd. de la Cultura, Amado Nervo s/n, CP 63190, Tepic, Nayarit, Mexico.
authors.forename: Norberto
authors.initials: N
authors.lastname: Vibanco-Pérez
authors.affiliation: Maestría en Salud Pública, Unidad Académica de Medicina, Universidad Autónoma de Nayarit, Tepic, Nayarit, Mexico.
authors.forename: Raquel Rocío
authors.initials: RR
authors.lastname: Hernández-Pacheco
authors.affiliation: Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas-Universidad Autónoma de Nayarit, Cd. de la Cultura, Amado Nervo s/n, CP 63190, Tepic, Nayarit, Mexico.
authors.forename: América Del Carmen
authors.initials: AD
authors.lastname: Castro-Zambrano
authors.affiliation: Clínica de Reumatología, Servicio de Medicina Interna, Instituto Mexicano del Seguro Social HGZ No. 1, Tepic, Nayarit, Mexico.
authors.forename: Liliana
authors.initials: L
authors.lastname: Ortiz-Martínez
authors.affiliation: Unidad Académica de Ciencias Químico Biológicas y Farmacéuticas-Universidad Autónoma de Nayarit, Cd. de la Cultura, Amado Nervo s/n, CP 63190, Tepic, Nayarit, Mexico. jzambran44@gmail.com.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Zambrano-Zaragoza
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000906:Antibodies / Q000097:blood*; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D050797:STAT4 Transcription Factor / Q000235:genetics*; D018417:Th1 Cells / Q000166:cytology; D058504:Th17 Cells / Q000166:cytology
chemical_list: D000906:Antibodies; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; C487763:cyclic citrullinated peptide
keywords: Biomarkers; Case–control study; Polymorphism; Rheumatoid arthritis; SNP