PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.
Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.
Programa Internacional del ICB, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, JAL, Mexico.
Maria Guadalupe
MG
Zavala-Cerna
Unidad de Investigación en Epidemiología Clínica, Hospital de Especialidades, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Norma Guadalupe
NG
Gonzalez-Montoya
Programa Internacional del ICB, Facultad de Medicina, Universidad Autónoma de Guadalajara, Guadalajara, JAL, Mexico ; Unidad de Investigación en Epidemiología Clínica, Hospital de Especialidades, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Arnulfo
A
Nava
Unidad de Investigación en Epidemiología Clínica, Hospital de Especialidades, Centro Médico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Jorge I
JI
Gamez-Nava
División de Medicina Molecular del Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Maria Cristina
MC
Moran-Moguel
División de Medicina Molecular del Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Roberto Carlos
RC
Rosales-Gomez
División de Medicina Molecular del Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Susan Andrea
SA
Gutierrez-Rubio
División de Medicina Molecular del Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Jose
J
Sanchez-Corona
Departamento de Medicina Interna-Reumatología del Hospital General Regional No. 110, Instituto Mexicano del Seguro Social, Guadalajara, JAL, Mexico.
Laura
L
Gonzalez-Lopez
División de Genética, CIBO, IMSS and Instituto de Genética Humana, CUCS Universidad de Guadalajara, Guadalajara, JAL, Mexico.
Ingrid Patricia
IP
Davalos-Rodriguez
División de Investigación en Salud, UMAE, Hospital de Especialidades, CMNO, IMSS and Departamento de Fisiología, CUCS, Universidad de Guadalajara, Mexico.
Mario
M
Salazar-Paramo
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008800:Mexico; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012307:Risk Factors
D001323:Autoantibodies; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases