Implications of Peptidyl Arginine Deiminase 4 gene transcription and polymorphisms in susceptibility to rheumatoid arthritis in an Iranian population.
Genetic association
Peptidyl arginine deiminase 4
Rheumatoid arthritis
Single nucleotide polymorphism
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
16 05 2023
16 05 2023
Historique:
received:
11
06
2022
accepted:
03
05
2023
medline:
18
5
2023
pubmed:
17
5
2023
entrez:
16
5
2023
Statut:
epublish
Résumé
Peptidyl arginine deiminase 4 (PADI4) has been implicated in Rheumatoid arthritis (RA) pathogenesis. Here we aimed to evaluate the association of PADI4 gene rs11203367 and rs1748033 single nucleotide polymorphisms (SNPs) with RA proneness. The mRNA expression of PADI4 was determined in the whole blood samples. The genotyping of PADI4 polymorphisms was conducted using allelic discrimination TaqMan genotyping Real-time PCR. The alleles and genotypes of rs11203367 polymorphism were not associated with susceptibility to RA risk. The T allele (OR = 1.58, 95%CI: 1.21-2.04, P = 0.0005), TT genotype (OR = 2.79, 95%CI: 1.53-5.06, P = 0.0007), TC genotype (OR = 1.52, 95%CI: 1.04-2.23, P = 0.0291), dominant (OR = 1.72, 95%CI: 1.19-2.47, P = 0.0034) and recessive (OR = 2.19, 95%CI: 1.25-3.82, P = 0.0057) models of rs1748033 SNP were associated with higher risk of RA. There was a significant upregulation of PADI4 mRNA in the RA patients compared to controls. mRNA expression of PADI4 had significantly positive correlation with anti-CCP level (r = 0.37, P = 0.041), RF level (r = 0.39, P = 0.037), and CRP level (r = 0.39, P = 0.024). PADI4 gene rs1748033 SNP was associated with increased RA risk. This polymorphism might affect the RA pathogenesis regardless of impressing the levels of PADI-4 in serum.
Sections du résumé
BACKGROUND
Peptidyl arginine deiminase 4 (PADI4) has been implicated in Rheumatoid arthritis (RA) pathogenesis. Here we aimed to evaluate the association of PADI4 gene rs11203367 and rs1748033 single nucleotide polymorphisms (SNPs) with RA proneness.
METHODS
The mRNA expression of PADI4 was determined in the whole blood samples. The genotyping of PADI4 polymorphisms was conducted using allelic discrimination TaqMan genotyping Real-time PCR.
RESULTS
The alleles and genotypes of rs11203367 polymorphism were not associated with susceptibility to RA risk. The T allele (OR = 1.58, 95%CI: 1.21-2.04, P = 0.0005), TT genotype (OR = 2.79, 95%CI: 1.53-5.06, P = 0.0007), TC genotype (OR = 1.52, 95%CI: 1.04-2.23, P = 0.0291), dominant (OR = 1.72, 95%CI: 1.19-2.47, P = 0.0034) and recessive (OR = 2.19, 95%CI: 1.25-3.82, P = 0.0057) models of rs1748033 SNP were associated with higher risk of RA. There was a significant upregulation of PADI4 mRNA in the RA patients compared to controls. mRNA expression of PADI4 had significantly positive correlation with anti-CCP level (r = 0.37, P = 0.041), RF level (r = 0.39, P = 0.037), and CRP level (r = 0.39, P = 0.024).
CONCLUSION
PADI4 gene rs1748033 SNP was associated with increased RA risk. This polymorphism might affect the RA pathogenesis regardless of impressing the levels of PADI-4 in serum.
Identifiants
pubmed: 37193992
doi: 10.1186/s12920-023-01532-9
pii: 10.1186/s12920-023-01532-9
pmc: PMC10186752
doi:
Substances chimiques
Protein-Arginine Deiminase Type 4
EC 3.5.3.15
PADI4 protein, human
EC 3.5.3.15
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
104Informations de copyright
© 2023. The Author(s).
Références
Rheumatol Int. 2007 Jul;27(9):827-33
pubmed: 17265154
Mod Rheumatol. 2013 Jan;23(1):50-60
pubmed: 22552437
Hum Immunol. 2017 Sep;78(9):553-558
pubmed: 28551357
Iran J Allergy Asthma Immunol. 2015 Jun;14(3):255-60
pubmed: 26546893
Arthritis Rheum. 2004 Apr;50(4):1117-21
pubmed: 15077293
J Gene Med. 2020 Sep;22(9):e3204
pubmed: 32333475
Clin Rheumatol. 2016 Apr;35(4):961-71
pubmed: 26474773
Bioessays. 2003 Nov;25(11):1106-18
pubmed: 14579251
Autoimmun Rev. 2010 Jan;9(3):158-60
pubmed: 19540364
Ann Rheum Dis. 2011 Mar;70(3):512-5
pubmed: 21062850
Gene. 2019 Jun 20;702:8-16
pubmed: 30904715
J Cell Physiol. 2019 Jul;234(7):10018-10031
pubmed: 30536757
Rheumatology (Oxford). 2005 Oct;44(10):1263-6
pubmed: 15998632
N Engl J Med. 2011 Dec 8;365(23):2205-19
pubmed: 22150039
Rheumatology (Oxford). 2006 Jul;45(7):804-7
pubmed: 16449362
Nat Genet. 2003 Aug;34(4):395-402
pubmed: 12833157
Clin Rev Allergy Immunol. 2013 Oct;45(2):170-9
pubmed: 23288628
Cell Res. 2005 Feb;15(2):97-8
pubmed: 15740637
Am J Hum Genet. 2005 Dec;77(6):1044-60
pubmed: 16380915
Ann Rheum Dis. 2010 Apr;69(4):666-70
pubmed: 19470526
Arthritis Rheum. 2005 Oct;52(10):3054-7
pubmed: 16200584
Immunol Lett. 2015 Feb;163(2):214-20
pubmed: 25562673
J Res Med Sci. 2021 Mar 31;26:22
pubmed: 34221051
Mediterr J Rheumatol. 2021 Dec 27;32(4):324-330
pubmed: 35128324
Life Sci. 2021 Mar 15;269:119034
pubmed: 33453247
Clin Rheumatol. 2020 Dec;39(12):3555-3569
pubmed: 32445089
Mayo Clin Proc. 2006 Jan;81(1):94-101
pubmed: 16438485
Int J Rheum Dis. 2023 Feb;26(2):259-266
pubmed: 36302513
Clin Rheumatol. 2020 Aug;39(8):2267-2279
pubmed: 32170488
Scand J Rheumatol. 2005 May-Jun;34(3):212-5
pubmed: 16134727
J Coll Physicians Surg Pak. 2012 Nov;22(11):711-5
pubmed: 23146852
Ann Rheum Dis. 2011 Aug;70(8):1468-70
pubmed: 21586440
Arthritis Rheum. 2006 Jan;54(1):90-6
pubmed: 16385500
Acta Reumatol Port. 2016 Oct-Dec;41(4):338-343
pubmed: 27182695
J Hum Genet. 2008;53(2):163-173
pubmed: 18087673
Nat Genet. 2022 Nov;54(11):1640-1651
pubmed: 36333501