Effects of Genetic Polymorphisms of Programmed Cell Death-1 in Susceptibility with Rheumatoid Arthritis in Najaf Population
DOI:
https://doi.org/10.36320/ajb/v11.i3.11866Keywords:
Rheumatoid arthritis, PD1, rs11568821, RFLP-PCR, ACCPAbstract
Background: The prevalence of Rheumatoid Arthritis (RA) has been raised in Iraq. The medical costs of such increased prevalence are high. Global studies have revealed polymorphisms of PD1 (Program Death 1) gene to be associated with Rheumatoid Arthritis (RA). This polymorphism can cause changes in various metabolic variables. Methods: The current study consists of 100 RA patients and 100 healthy control individuals. Variable parameters data included Anti-Cyclic cytrulinated peptide expression (ACCP), Rheumatoid factor (RF), C-Reactive Protein (CRP) in serum and Erythrocytes sedimentation rate (ESR) leveles. Genotyping of PD1gene polymorphism is carried out by RFLP-PCR. Various statistical analyses were applied to analyze the data.
Results: The estimation of immunological and biochemical data pointed out significant differences in Gender, RF, ACCP, CRP, ESR and age in RA when compared with those of the control group. The genotyping results were found to be consistent with Hardy-Weinberg equilibrium. The analysis of the genotype distribution under various inheritance models highlighted significant differences in SNP of PD1 gene polymorphism among RA patients when compared with the control group under the dominant homozygote, heterozygote and recessive homozygote. The genotype and allele frequencies of the PD1 SNP rs11568821; genotype GA was significantly increased in RA compared with controls (45% and 24%, respectively) (P=0.0020),(OR =2.5909),(95% CI 1.4-4.7) . Subjects who carried A allele were significantly more likely to develop RA three folds AA(OR=3.3529, 95% CI=1.1691-9.6160, P=0.0244). Clinical characteristics were observed to change significantly with respect to the genotype distribution of the investigated SNP. Conclusion: PD1 gene polymorphisms (rs11568821) is implicated in the pathogenesis of Rheumatoid arthritis in Najaf population.
Downloads
References
Aletaha, D., Neogi, T., Silman, A. J., Funovits, J., Felson, D. T., Bingham III, C. O., ... & Combe, B. (2010). 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis & Rheumatism, 62(9), 2569-2581.
Bartok, B., & Firestein, G. S. (2010). Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunological reviews, 233(1), 233-255.
Chou, C. T., Liao, H. T., Chen, C. H., Chen, W. S., Wang, H. P., & Su, K. Y. (2007). The clinical application of anti-CCP in rheumatoid arthritis and other rheumatic diseases. Biomarker insights, 2, 117727190700200007.
Dai, S., Jia, R., Zhang, X., Fang, Q., & Huang, L. (2014). The PD-1/PD-Ls pathway and autoimmune diseases. Cellular immunology, 290(1), 72-79.
Do Canto, L. M., Farias, T. D. J., Medeiros, M. D., Coêlho, C. C., Sereia, A. F. R., de Carlos Back, L. K. F., ... & de Souza, I. R. (2016). Association of PDCD1 polymorphism to systemic lupus erythematosus and rheumatoid arthritis susceptibility. Revista Brasileira de Reumatologia (English Edition), 56(6), 483-489.
Dolhain, R. J., van der Heiden, A. N., ter Haar, N. T., Breedveld, F. C., & Miltenburg, A. M. (1996). Shift toward T lymphocytes with a T helper 1 cytokine-secretion profile in the joints of patients with rheumatoid arthritis. Arthritis & Rheumatism, 39(12), 1961-1969.
Fedetz, M. (2009). Asociación de genes candidatos a esclerosis múltiple: estudio funcional del gen de la IL-2.
Gibofsky, A. (2012). Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. The American journal of managed care, 18(13 Suppl), S295-302.
Ibrahim, W. S., & Abdelghani, S. E. (2018). Programmed cell death 1 gene polymorphism association with activity and severity of systemic lupus erythematosus and rheumatoid arthritis in Egyptian patients. Tanta Medical Journal, 46(3), 225.
Jawad, A. A., Addoos, S. A., & Tarish, H. R. (2017). Association between gene polymorphism in programmed cell death 1 (PD1. 1) and susceptibility for rheumatoid arthritis in an Iraqi patients? Case control study. journal of kerbala university, 15(4), 19-25.
Prasannavar, D. J., Yeola, A., Pradhan, V., Patwardhan, M., Rajadhyaksha, A., & Ghosh, K. (2014). Distribution of HLA-DRβ1 alleles among well-characterized rheumatoid arthritis patients from Western India. Rheumatology international, 34(5), 705-708.
Prokunina L, Padyukov L, Bennet A, de Faire U, Wiman B, et al. (2004) Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum 50(6): 1770-1773.
Prokunina, L., Castillejo-López, C., Öberg, F., Gunnarsson, I., Berg, L., Magnusson, V., ... & Bolstad, A. I. (2002). A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nature genetics, 32(4), 666.
Scott, D.L., Wolfe, F. and Huizinga, T.W.J., (2010). Rheumatoid arthritis. Lancet, 376: 1094–1108.
Siwiec, A., Majdan, M., Ciesielka, M., Mlak, R., & Krajka, T. (2015). SAT0063 Association of the Programmed Death 1 Gene Polymorphism with the Development of Rheumatoid Arthritis in the Population of South-Eastern Poland.
Thompson, Margaret W., Roderick R. McInnes, and Huntington F. Willard. (1991). Thompson & Thompson genetics in medicine. Fifth ed. Philadelphia: W. B. Saunders,.
Thyberg, I., Dahlström, Ö., & Thyberg, M. (2009). Factors related to fatigue in women and men with early rheumatoid arthritis: the Swedish TIRA study. Journal of rehabilitation medicine, 41(11), 904-912.
Tseng, C. C., Lin, Y. Z., Lin, C. H., Li, R. N., Tsai, W. C., Ou, T. T., ... & Yen, J. H. (2019). Genetic and Epigenetic Alteration of the Programmed Cell Death 1 (PDCD 1) in Rheumatoid Arthritis. European journal of clinical investigation, e13094.
Wang, S. L., Chang, C. H., Hu, L. Y., Tsai, S. J., Yang, A. C., & You, Z. H. (2014). Risk of developing depressive disorders following rheumatoid arthritis: a nationwide population-based study. PloS one, 9(9), e107791.
Zhang, J., & Braun, M. Y. (2014). PD-1 deletion restores susceptibility to experimental autoimmune encephalomyelitis in miR-155-deficient mice. International immunology, 26(7), 407-415.
Zou, Y., Zhang, Z., Liu, Y., Liu, D., & Xu, W. (2017). Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: a meta-analysis. Medicine, 96(35).
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Rashad Kadhim Mahmood Al-Akhras, Alaa Shakir Al-Nahi
This work is licensed under a Creative Commons Attribution 4.0 International License.
which allows users to copy, create extracts, abstracts, and new works from the Article, alter and revise the Article, and make commercial use of the Article (including reuse and/or resale of the Article by commercial entities), provided the user gives appropriate credit (with a link to the formal publication through the relevant DOI), provides a link to the license, indicates if changes were made and the licensor is not represented as endorsing the use made of the work.
