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PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico
Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498032/ https://www.ncbi.nlm.nih.gov/pubmed/36135205 http://dx.doi.org/10.3390/cimb44090293 |
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author | Matuz-Flores, Mónica Guadalupe Rosas-Rodríguez, Jesús Alfredo Tortoledo-Ortiz, Orlando Muñoz-Barrios, Salvador Martínez-Bonilla, Gloria Esther Hernández-Bello, Jorge Baños-Hernández, Christian Johana Pacheco-Tena, Cesar Sánchez-Zuno, Gabriela Athziri Panduro-Espinoza, Beatriz Muñoz-Valle, José Francisco |
author_facet | Matuz-Flores, Mónica Guadalupe Rosas-Rodríguez, Jesús Alfredo Tortoledo-Ortiz, Orlando Muñoz-Barrios, Salvador Martínez-Bonilla, Gloria Esther Hernández-Bello, Jorge Baños-Hernández, Christian Johana Pacheco-Tena, Cesar Sánchez-Zuno, Gabriela Athziri Panduro-Espinoza, Beatriz Muñoz-Valle, José Francisco |
author_sort | Matuz-Flores, Mónica Guadalupe |
collection | PubMed |
description | Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the PAD4 activity in patients with RA from Mexico. Methodology: 100 RA patients and 100 control subjects (CS) were included. Genotyping was performed by PCR-RFLP method, PADI4 mRNA expression was quantified by real-time PCR, the contribution of PADI4 alleles (PADI4_89 G>A, PADI4_90 T>C, and PADI4_92 G>C) to mRNA expression by the ASTQ method, and PAD4 activity by HPLC. Also, the anti-CCP and anti-PADI4 antibodies were quantified by ELISA. Results: The three PADI4 polymorphisms were associated with RA susceptibility (OR = 1.72, p = 0.005; OR = 1.62; p = 0.014; OR = 1.69; p = 0.009; respectively). The 89G, 90T, and 92G alleles have a higher relative contribution to PADI4 mRNA expression from RA patients than 89A, 90C, and 92C alleles in RA patients. Moreover, the GTG/GTG haplotype was associated with RA susceptibility (OR = 2.86; p = 0.024). The GTG haplotype was associated with higher PADI4 mRNA expression (p = 0.04) and higher PAD4 enzymatic activity (p = 0.007) in RA patients. Conclusions: The evaluated polymorphisms contribute to PADI4 mRNA expression and the enzymatic activity of PAD4 in leukocytes. Therefore, the GTG haplotype is a genetic risk factor for RA in western Mexico, and is associated with increased PADI4 mRNA expression and higher PAD4 activity in these patients. |
format | Online Article Text |
id | pubmed-9498032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-94980322022-09-23 PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico Matuz-Flores, Mónica Guadalupe Rosas-Rodríguez, Jesús Alfredo Tortoledo-Ortiz, Orlando Muñoz-Barrios, Salvador Martínez-Bonilla, Gloria Esther Hernández-Bello, Jorge Baños-Hernández, Christian Johana Pacheco-Tena, Cesar Sánchez-Zuno, Gabriela Athziri Panduro-Espinoza, Beatriz Muñoz-Valle, José Francisco Curr Issues Mol Biol Article Citrullination is catalyzed by the peptidyl arginine deiminase 4 (PAD4) enzyme, encoded by the PADI4 gene. Increased PAD4 activity promotes the onset and progression of rheumatoid arthritis (RA). This study aimed to evaluate the association of PADI4 haplotypes with RA risk, mRNA expression, and the PAD4 activity in patients with RA from Mexico. Methodology: 100 RA patients and 100 control subjects (CS) were included. Genotyping was performed by PCR-RFLP method, PADI4 mRNA expression was quantified by real-time PCR, the contribution of PADI4 alleles (PADI4_89 G>A, PADI4_90 T>C, and PADI4_92 G>C) to mRNA expression by the ASTQ method, and PAD4 activity by HPLC. Also, the anti-CCP and anti-PADI4 antibodies were quantified by ELISA. Results: The three PADI4 polymorphisms were associated with RA susceptibility (OR = 1.72, p = 0.005; OR = 1.62; p = 0.014; OR = 1.69; p = 0.009; respectively). The 89G, 90T, and 92G alleles have a higher relative contribution to PADI4 mRNA expression from RA patients than 89A, 90C, and 92C alleles in RA patients. Moreover, the GTG/GTG haplotype was associated with RA susceptibility (OR = 2.86; p = 0.024). The GTG haplotype was associated with higher PADI4 mRNA expression (p = 0.04) and higher PAD4 enzymatic activity (p = 0.007) in RA patients. Conclusions: The evaluated polymorphisms contribute to PADI4 mRNA expression and the enzymatic activity of PAD4 in leukocytes. Therefore, the GTG haplotype is a genetic risk factor for RA in western Mexico, and is associated with increased PADI4 mRNA expression and higher PAD4 activity in these patients. MDPI 2022-09-16 /pmc/articles/PMC9498032/ /pubmed/36135205 http://dx.doi.org/10.3390/cimb44090293 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Matuz-Flores, Mónica Guadalupe Rosas-Rodríguez, Jesús Alfredo Tortoledo-Ortiz, Orlando Muñoz-Barrios, Salvador Martínez-Bonilla, Gloria Esther Hernández-Bello, Jorge Baños-Hernández, Christian Johana Pacheco-Tena, Cesar Sánchez-Zuno, Gabriela Athziri Panduro-Espinoza, Beatriz Muñoz-Valle, José Francisco PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico |
title | PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico |
title_full | PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico |
title_fullStr | PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico |
title_full_unstemmed | PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico |
title_short | PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico |
title_sort | padi4 haplotypes contribute to mrna expression, the enzymatic activity of peptidyl arginine deaminase and rheumatoid arthritis risk in patients from western mexico |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9498032/ https://www.ncbi.nlm.nih.gov/pubmed/36135205 http://dx.doi.org/10.3390/cimb44090293 |
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