Allelic expression of 89G/A, 90T/C and 92G/C PADI4 polymorphisms in rheumatoid arthritis
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1
Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de Biología Molecular y Genómica, Mexico
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2
Unidad Académica de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Mexico
Introduction: Rheumatoid Arthritis (RA) is an inflammatory joint disease of unknown etiology where genetic factors have been associated with the onset and progression of the disease (1). Polymorphisms 89G/A, 90T/C and 92G/C, including the haplotype (GTG) of PADI4 gene, have been associated with RA susceptibility in several populations (2,3). However, the allelic expression of these polymorphisms has not been reported. Aim: To assess the allelic expression of 89G/A, 90T/C and 92G/C PADI4 polymorphisms in RA. Methods: RA patients classified according to the 1987 ACR criteria and control subjects (CS), adjusted by age and sex, were included. The allelic expression was determined by ASTQ method in heterozygotes of 89G/A, 90T/C and 92G/C PADI4 polymorphisms and mRNA expression of the PADI4 gene was determined with qPCR in samples classified as homozygotes for the ACC and GTG haplotypes. The data was analyzed with STATA v 9.2 software and p<0.05 was reported as statistically significant. Results: We found a high expression of 89A, 90C and 92C alleles in CS compared with RA patients (62.3% vs 46.7%, 55.6% vs 27.7% and 84.7% vs 43.9%, respectively) and a high expression of 89G, 90T and 92G alleles in RA patients compared with CS (53.3% vs 37.7%, 72.3% vs 44.4% and 56.1% vs 15.3%, respectively). Also, we observed in RA patients that GTG haplotype carriers has 3.29-fold more expression that ACC haplotype carriers (p<0.001). Conclusion: This study revealed that the 89G, 90T and 92G alleles and the GTG susceptibility haplotype was associated with increased gene expression in RA.
References
1. McInnes IB, Schett G. The pathogenesis of rheumatoid arthritis. N Engl J Med. 2011;365(23):2205-19.
2. Anzilotti C, Pratesi F, Tommasi C, Migliorini P. Peptidylarginine deiminase 4 and citrullination in health and disease. Autoimmun Rev. 2010;9(3):158-60.
3. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003;34(4):395-402.
Keywords:
allelic expression,
Gene Expression,
Haplotypes,
Peptidylarginine deiminase type 4,
Rheumatoid arthritis
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Muñoz-Barrios
S,
Angel-Chávez
LI,
Palafox-Sánchez
CA,
Oregon-Romero
E,
Parra-Rojas
I,
Reyes-Castillo
Z,
Vázquez-Villamar
M and
Muñoz-Valle
JF
(2013). Allelic expression of 89G/A, 90T/C and 92G/C PADI4 polymorphisms in rheumatoid arthritis.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00245
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Received:
12 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. José F Muñoz-Valle, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Departamento de Biología Molecular y Genómica, Guadalajara, Jalisco, 44340, Mexico, biologiamolecular@hotmail.com