ASSOCIATION OF TUMOUR NECROSIS FACTOR-ALPHA -308 G/A PROMOTER POLYMORPHISM WITH SUSCEPTIBILITY AND DISEASE PROFILE OF RHEUMATOID ARTHRITIS

Sadia khurshid, Alam Zeb, Saira Bano, Uzma Rasheed, Shazia Zammurrad, Muhammad Sufyan Khan, Tayyaba Khursheed, Wajahat Aziz

Abstract


Background: Single nucleotide polymorphism underlying the auto-immune process governing the pathologic manifestations of rheumatoid arthritis has been the focus of study for quite a while.  TNF-alpha -308 G/A promoter polymorphism has been reported to be responsible for a number of manifestations of rheumatoid arthritis. methods: This case-control study was conducted at the department of Rheumatology at Pakistan Institute of Medical Sciences Islamabad from 9th May to 9th August 2019 with a focus to determine the Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. One hundred and fifty cases with diagnosed rheumatoid arthritis and 150 age and gender matched controls were enrolled in the study. Their genotyping was done for tumour necrosis factor-alpha -308 G/A promoter polymorphism. Results: The genotypic analysis showed that GG genotype was the most common genotype found in 118 cases (78.66%) followed by GA (18.66%) and AA genotype (2.6%) p=0.0096 in both cases and controls. Overall, G allele was more common than A in both cases and controls pointing towards the preponderance of G genotype in our population. (p=0.003). However, the GA genotype and A allelotype was more common among cases with rheumatoid arthritis (p <0.05). No significant association of G/A polymorphism with smoking and gender, however, within gender, males had a significantly more expression of the GA genotype and A allelotype (p <0.05). Conclusion: There is a significantly more expression of the GA genotype and the A allelotype of the TNF-alpha -308 G/A promoter gene in rheumatoid arthritis patients in our population. Similarly, more males, compared to females have increased expression of the GA genotype as well as the A allelotype.

Keywords: Rheumatoid Arthritis; Tumour necrosis factor alpha; Auto-immune disease; Single nucleotide polymorphism; Allelotype

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References


Lambrecht V, Jans L, Huysse W, Verstraete K. Radiographic findings in rheumatoid arthritis. In Seminarie postgraduate radiologie Vlaamse Universiteiten (PRVU) 2011.

Goldring SR. Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology (Oxfored) 2003;42(suppl_2):ii11–6.

Karmakar S, Kay J, Gravallese EM. Bone damage in rheumatoid arthritis: mechanistic insights and approaches to prevention. Rheum Dis Clin North Am 2010;36(2):385–404.

Silman AJ, Pearson JE. Epidemiology and genetics of rheumatoid arthritis. Arthritis Res Ther 2002;4(Suppl 3):S265.

Stahl EA, Wegmann D, Trynka G, Gutierrez-Achury J, Do R, Voight BF, et al. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis. Nat Genet 2012;44(5):483–9.

Arshad M, Bhatti A, John P, Jalil F, Williams RO. Association of rs182429 variant in TAGAP with rheumatoid arthritis in Pakistani population. Meta Gene 2017;14:59–63.

Wegner N, Lundberg K, Kinloch A, Fisher B, Malmström V, Feldmann M, et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev 2010;233(1):34–54.

Stoffer MA, Schoels MM, Smolen JS, Aletaha D, Breedveld FC, Burmester G, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update. Ann Rheum Dis 2016;75(1):16–22.

Rodríguez-Elías AK, Maldonado-Murillo K, López-Mendoza LF, Ramírez-Bello J. [Genetics and genomics in rheumatoid arthritis (RA): an update]. Gac Med Mex 2016;152(2):218–27.

García-Bermúdez M, López-Mejías R, González-Juanatey C, Castañeda S, Miranda-Filloy J, Blanco R, et al. Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with cardiovascular disease in patients with rheumatoid arthritis. Scand J Rheumatol 2012;41(5):350–3.

Bax M, van Heemst J, Huizinga TWJ, Toes REM. Genetics of rheumatoid arthritis: what have we learned? Immunogenetics 2011;63(8):459–66.

Gambhir D, Lawrence A, Aggarwal A, Misra R, Mandal SK, Naik S. Association of tumor necrosis factor alpha and IL-10 promoter polymorphisms with rheumatoid arthritis in North Indian population. Rheumatol Int 2010;30(9):1211–7.

Chen R, Fang M, Cai Q, Duan S, Lv K, Cheng N, et al. Tumor necrosis factor alpha- 308 polymorphism is associated with rheumatoid arthritis in Han population of Eastern China. Rheumatol Int 2007;28(2):121–6.

Raina P, Matharoo K, Kumar A, Sarangal P, Sharma R,Bhanwer AJS. Association of Tumor Necrosis Factor-Alpha -308 G>A Polymorphism With Rheumatoid Arthritis in Two North Indian Cohorts. Arch Rheumatol 2014;29(4):241–9.

Hashimoto R, Yoshida M, Ozaki N, Yamanouchi Y, Iwata N, Suzuki T, et al. Association analysis of the- 308G> A promoter polymorphism of the tumor necrosis factor alpha (TNF-α) gene in Japanese patients with schizophrenia. J Neural Transm 2004;111(2):217–21.

Kang SW, Kim SK, Han YR, Hong D, Chon J, Chung JH, et al. Promoter Polymorphism (-308G/A) of Tumor Necrosis Factor-Alpha (TNF-α) Gene and Asthma Risk: An Updated Meta-Analysis. Genet Test Mol Biomark. 2019;23(6):363–72.

Varljen T, Rakic O, Sekulovic G, Jekic B, Maksimovic N, Janevski MR, et al. Association between Tumor Necrosis Factor-α Promoter -308 G/A Polymorphism and Early Onset Sepsis in Preterm Infants. Tohoku J Exp Med 2019;247(4):259–64.

Huang X, Qin S, Liu Y, Tao L, Jiang H. Associations of tumor necrosis factor-α polymorphisms with the risk of colorectal cancer: A meta-analysis. Biosci Rep 2019;39(1):BSR20181750.

Agliardi C, Guerini FR, Zanzottera M, Riboldazzi G, Zangaglia R, Bono G, et al. TNF-α -308 G/A and -238 G/A promoter polymorphisms and sporadic Parkinson’s disease in an Italian cohort. J Neurol Sci 2018;385:45–8.

Umapathy D, Krishnamoorthy E, Mariappanadar V, Viswanathan V, Ramkumar KM. Increased levels of circulating (TNF-α) is associated with (-308G/A) promoter polymorphism of TNF-α gene in Diabetic Nephropathy. Int J Biol Macromol 2018;107(Pt B):2113–21.

Manolova I, Ivanova M, Stoilov R, Rashkov R, Stanilova S. Association of single nucleotide polymorphism at position -308 of the tumor necrosis factor-alpha gene with ankylosing spondylitis and rheumatoid arthritis. Biotechnol Biotechnol Equip 2014;28(6):1108–14.

Aranda F, Perés Wingeyer SD, Schneeberger E, Valerio M, Saint Martin E, Dal Pra F, et al. The -308 G/A polymorphism in the tumor necrosis factor-α gene is not associated with development and progression of rheumatoid arthritis in Argentinean patients. Int J Rheum Dis 2016;19(5):476–81.

Zeng Z, Duan Z, Zhang T, Wang S, Li G, Gao J, et al. Association between tumor necrosis factor-α (TNF-α) promoter -308 G/A and response to TNF-α blockers in rheumatoid arthritis: a meta-analysis. Mod Rheumatol 2013;23(3):489–95.

Mosaad YM, Abdelsalam A, El-Bassiony SR. Association of tumour necrosis factor-alpha -308 G/A promoter polymorphism with susceptibility and disease profile of rheumatoid arthritis. Int J Immunogenet 2011;38(5):427–33


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