TY - JOUR
T1 - PADI4 Haplotypes Contribute to mRNA Expression, the Enzymatic Activity of Peptidyl Arginine Deaminase and Rheumatoid Arthritis Risk in Patients from Western Mexico.
AU - Matuz-Flores, Mónica Guadalupe
AU - Rosas-Rodríguez, Jesús Alfredo
AU - Tortoledo-Ortiz, Orlando
AU - Muñoz-Barrios, Salvador
AU - Martínez-Bonilla, Gloria Esther
AU - Hernández-Bello, Jorge
AU - Baños-Hernández, Christian Johana
AU - Pacheco-Tena, Cesar
AU - Sánchez-Zuno, Gabriela Athziri
AU - Panduro-Espinoza, Beatriz
AU - Muñoz-Valle, José Francisco
PY - 2022/9/16
Y1 - 2022/9/16
N2 - 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.
AB - 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.
U2 - 10.3390/cimb44090293
DO - 10.3390/cimb44090293
M3 - Artículo
C2 - 36135205
VL - 44
SP - 4268
EP - 4281
JO - Current issues in molecular biology
JF - Current issues in molecular biology
SN - 1467-3037
IS - 9
ER -