[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: Volume 2, Issue 2 (Journal of Clinical and Basic Research(JCBR) 2018) ::
jcbr 2018, 2(2): 11-16 Back to browse issues page
Association Assessment of Peptidylarginine Deiminase Type 4 (PADI4) rs1748033 polymorphism and susceptibility to rheumatoid arthritis in Gorgan, Northeast of Iran
Aytekin Aghchelli , Yaghoub Yazdani , Hadi Bazzazi , Mehrdad Aghaei
Abstract:   (43 Views)
Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease in which both genetic and environmental factors could be involved. Peptidyl arginine deiminase type IV (PADI4) is an enzyme responsible for the posttranslational conversion of arginine residues into citrulline. The association between PADI4 single nucleotide polymorphisms (SNPs) and RA susceptibility have been reported. Here, we aimed to assess the association of PADI4-104 (rs1748033) variant with the susceptibility to RA in an Iranian population in northeast of Iran. Materials and methods: A total of 130 RA patients and 128 age- and sex-matched healthy donors were recruited. The amplification-refractory mutation system with allele specific primers was used to detect PADI4-104 SNP. Disease activity was calculated using Disease Activity Scale 28a. SPSS 22.0 and SNPstat online software were used to analyze data using relevant statistical tests. Results: The CC genotype was more frequent in healthy subjects compared to RA patients. Setting the CC genotype as the reference, the TT genotype was significantly associated with increased risk of RA [OR = 2.11, 95% CI (1.45–3.07), P-value = 0.0001]. Moreover, no significant association was observed between genotypes and the disease activity score (P=0.154). Conclusions: The present study suggests that the PADI4-104 genetic variants are associated with RA susceptibility but not with the disease activity. While this is the first time to report such association in an Iranian population in northeast of Iran, further studies are required to confirm these findings.
Keywords: Amplification-refractory mutation system, Peptidylarginine Deiminase Type 4, Rheumatoid arthritis, Single nucleotide polymorphism
Full-Text [PDF 412 kb]   (23 Downloads)    
Type of Study: Research | Subject: Statistics and epidemiology
Received: 2018/08/22 | Accepted: 2018/08/22 | Published: 2018/08/22
1. McInnes IB, Schett G. Pathogenetic insights from the treatment of rheumatoid arthritis. The Lancet. 2017;389(10086):2328-37. [DOI:10.1016/S0140-6736(17)31472-1]
2. Singh JA, Saag KG, Bridges SL, Akl EA, Bannuru RR, Sullivan MC, et al. 2015 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis & rheumatology. 2016;68(1):1-26. [DOI:10.1002/art.39480]
3. Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, et al. The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Annals of the rheumatic diseases. 2014. [DOI:10.1136/annrheumdis-2013-204627]
4. Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506(7488):376. [DOI:10.1038/nature12873]
5. Catrina AI, Deane KD, Scher JU. Gene, environment, microbiome and mucosal immune tolerance in rheumatoid arthritis. Rheumatology. 2014;55(3):391-402. [DOI:10.1093/rheumatology/keu469]
6. Nelson JL, Lambert NC. Rheumatoid arthritis: Forward and reverse inheritance—the yin and the yang. Nature Reviews Rheumatology. 2017;13(7):396. [DOI:10.1038/nrrheum.2017.88]
7. van Heemst J, Huizinga TJ, van der Woude D, Toes RE. Fine-mapping the human leukocyte antigen locus in rheumatoid arthritis and other rheumatic diseases: identifying causal amino acid variants? Current opinion in rheumatology. 2015;27(3):256-61. [DOI:10.1097/BOR.0000000000000165]
8. Lei C, Dongqing Z, Yeqing S, Oaks MK, Lishan C, Jianzhong J, et al. Association of the CTLA-4 gene with rheumatoid arthritis in Chinese Han population. European journal of human genetics. 2005;13(7):823. [DOI:10.1038/sj.ejhg.5201423]
9. Karlson EW, Chibnik LB, Cui J, Plenge RM, Glass RJ, Maher NE, et al. Associations between human leukocyte antigen, PTPN22, CTLA4 genotypes and rheumatoid arthritis phenotypes of autoantibody status, age at diagnosis and erosions in a large cohort study. Annals of the rheumatic diseases. 2008;67(3):358-63. [DOI:10.1136/ard.2007.071662]
10. Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, et al. STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. New England Journal of Medicine. 2007;357(10):977-86. [DOI:10.1056/NEJMoa073003]
11. Stahl EA, Raychaudhuri S, Remmers EF, Xie G, Eyre S, Thomson BP, et al. Genome-wide association study meta-analysis identifies seven new rheumatoid arthritis risk loci. Nature genetics. 2010;42(6):508. [DOI:10.1038/ng.582]
12. Bang S-Y, Han T-U, Choi C-B, Sung Y-K, Bae S-C, Kang C. Peptidyl arginine deiminase type IV (PADI4) haplotypes interact with shared epitope regardless of anti-cyclic citrullinated peptide antibody or erosive joint status in rheumatoid arthritis: a case control study. Arthritis research & therapy. 2010;12(3):R115. [DOI:10.1186/ar3051]
13. Suzuki A, Yamada R, Chang X, Tokuhiro S, Sawada T, Suzuki M, et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nature genetics. 2003;34(4):395. [DOI:10.1038/ng1206]
14. Harris ML, Darrah E, Lam GK, Bartlett SJ, Giles JT, Grant AV, et al. Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis. Arthritis & Rheumatology. 2008;58(7):1958-67. [DOI:10.1002/art.23596]
15. Van Venrooij WJ, Van Beers JJ, Pruijn GJ. Anti-CCP antibodies: the past, the present and the future. Nature Reviews Rheumatology. 2011;7(7):391. [DOI:10.1038/nrrheum.2011.76]
16. Vossenaar ER, Radstake TR, van der Heijden A, van Mansum MA, Dieteren C, de Rooij D-J, et al. Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Annals of the rheumatic diseases. 2004;63(4):373-81. [DOI:10.1136/ard.2003.012211]
17. Foulquier C, Sebbag M, Clavel C, Chapuy‐Regaud S, Al Badine R, Méchin MC, et al. Peptidyl arginine deiminase type 2 (PAD‐2) and PAD‐4 but not PAD‐1, PAD‐3, and PAD‐6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis & Rheumatology. 2007;56(11):3541-53. [DOI:10.1002/art.22983]
18. Iwamoto T, Ikari K, Nakamura T, Kuwahara M, Toyama Y, Tomatsu T, et al. Association between PADI4 and rheumatoid arthritis: a meta-analysis. Rheumatology. 2006;45(7):804-7. [DOI:10.1093/rheumatology/kel023]
19. Fransen J, Stucki G, van Riel PL. Rheumatoid arthritis measures: Disease Activity Score (DAS), Disease Activity Score‐28 (DAS28), Rapid Assessment of Disease Activity in Rheumatology (RADAR), and Rheumatoid Arthritis Disease Activity Index (RADAI). Arthritis Care & Research. 2003;49(S5). [DOI:10.1002/art.11407]
20. Mohammadi S, Sedighi S, Memarian A, Yazdani Y. Overexpression of interferon-γ and indoleamine 2, 3-dioxygenase in systemic lupus erythematosus: relationship with the disease activity. LaboratoriumsMedizin. 2017;41(1):41-7. [DOI:10.1515/labmed-2016-0076]
21. Barton A, Bowes J, Eyre S, Spreckley K, Hinks A, John S, et al. A functional haplotype of the PADI4 gene associated with rheumatoid arthritis in a Japanese population is not associated in a United Kingdom population. Arthritis & Rheumatology. 2004;50(4):1117-21. [DOI:10.1002/art.20169]
22. Ikari K, Kuwahara M, Nakamura T, Momohara S, Hara M, Yamanaka H, et al. Association between PADI4 and rheumatoid arthritis: a replication study. Arthritis & Rheumatology. 2005;52(10):3054-7. [DOI:10.1002/art.21309]
23. Hoppe B, Häupl T, Gruber R, Kiesewetter H, Burmester GR, Salama A, et al. Detailed analysis of the variability of peptidylarginine deiminase type 4 in German patients with rheumatoid arthritis: a case–control study. Arthritis research & therapy. 2006;8(2):R34. [DOI:10.1186/ar1889]
24. Martinez A, Valdivia A, Pascual-Salcedo D, Lamas JR, Fernandez-Arquero M, Balsa A, et al. PADI4 polymorphisms are not associated with rheumatoid arthritis in the Spanish population. Rheumatology. 2005;44(10):1263-6. [DOI:10.1093/rheumatology/kei008]
25. Hou S, Gao G-p, Zhang X-j, Sun L, Peng W-j, Wang H-f, et al. PADI4 polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis. Modern rheumatology. 2013;23(1):50-60. [DOI:10.3109/s10165-012-0639-4]
26. Du Y, Liu X, Guo J, Li R, Zhao Y, Li M, et al. Association between PADI4 gene polymorphisms and anti-cyclic citrullinated peptide antibody positive rheumatoid arthritis in a large Chinese Han cohort. Clinical and experimental rheumatology. 2014;32(3):377-82.
27. Lee YH, Bae S-C. Association between susceptibility to rheumatoid arthritis and PADI4 polymorphisms: a meta-analysis. Clinical rheumatology. 2016;35(4):961-71. [DOI:10.1007/s10067-015-3098-4]
28. Panati K, Pal S, Reddy VD. Association of single nucleotide polymorphisms (SNPs) of PADI4 gene with rheumatoid arthritis (RA) in Indian population. Genes & genetic systems. 2012;87(3):191-6. [DOI:10.1266/ggs.87.191]
29. Shamsian E, Azarian M, Akhlaghi M, Samaei M, Jamshidi AR, Assar S, et al. PADI4 Polymorphisms in Iranian Patients with Rheumatoid Arthritis. Acta reumatologica portuguesa. 2016;41(4):338-43.
30. Hashemi M, Zakeri Z, Taheri H, Bahari G, Taheri M. Association between peptidylarginine deiminase type 4 rs1748033 polymorphism and susceptibility to rheumatoid arthritis in Zahedan, Southeast Iran. Iranian Journal of Allergy, Asthma and Immunology. 2015;14(3):255-60.
Add your comments about this article
Your username or Email:


XML     Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Aghchelli A, Yazdani Y, Bazzazi H, Aghaei M. Association Assessment of Peptidylarginine Deiminase Type 4 (PADI4) rs1748033 polymorphism and susceptibility to rheumatoid arthritis in Gorgan, Northeast of Iran. jcbr. 2018; 2 (2) :11-16
URL: http://jcbr.goums.ac.ir/article-1-139-en.html

Volume 2, Issue 2 (Journal of Clinical and Basic Research(JCBR) 2018) Back to browse issues page
Journal of Clinical and Basic Research Journal of Clinical and Basic Research
Persian site map - English site map - Created in 0.05 seconds with 31 queries by YEKTAWEB 3755