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Genetic and expression changes in \(\hbox {TNF-}\upalpha \) as a risk factor for rheumatoid arthritis pathogenesis in northeast India

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Abstract

Antitumour necrosis factor-alpha \((\hbox {TNF-}\upalpha )\) therapy is used as a clinical intervention for rheumatoid arthritis (RA) but differences exist in response to the treatment which makes the candidature of the screening of \(\hbox {TNF-}\upalpha \) alteration(s) at genetic and expression levels an important agenda prior to treatment. This study aims to determine the associative role of \(\hbox {TNF-}\upalpha \) –308G/A polymorphism and differential expression of \(\hbox {TNF-}\upalpha \) in the pathogenesis of RA. A case–control study where a total of 126 RA patients were enrolled based on ACR-EULAR (2010) criteria, along with 160 community matched age and sex controls over a period of three years. The differential expression level of \(\hbox {TNF-}\upalpha \) mRNA and protein level was studied and \(\hbox {TNF-}\upalpha \) –308G/A polymorphism was screened by T-ARMS PCR assay. All statistical analysis was performed using SPSS software. mRNA expression level of \(\hbox {TNF-}\upalpha \) was upregulated in RA cases (avg. \(15.85\pm 9.52\) fold) compared to control. \(\hbox {TNF-}\upalpha \) protein level was found to be higher in RA cases (\(28.62\pm 7.17\) pg/mL) compared to control (\(23.14\pm 6.91\) pg/mL). \(\hbox {TNF-}\upalpha \) –308 variant GA genotype was higher in RA (46.03%) than in control (25%). The presence of \(\hbox {TNF-}\upalpha \) –308 variant A allele was associated with increased risk of RA susceptibility (odds ratio \((\hbox {OR})=2.559\) at 95% confidence interval (CI), \(P < 0.001\)) but not severity (\(\hbox {OR}=1.617\) at 95% CI, \(P=0.571\)). The presence of –308 variant genotype was associated with a higher \(\hbox {TNF-}\upalpha \) mRNA and protein expression. The presence of \(\hbox {TNF-}\upalpha \) –308A allele is associated with increased risk of RA susceptibility and differential \(\hbox {TNF-}\upalpha \) expression, and has prognostic significance. Association of higher \(\hbox {TNF-}\upalpha \) pro-inflammatory cytokine levels with northeast Indian patients makes them suitable subjects for \(\hbox {anti-TNF-}\upalpha \) therapy.

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Acknowledgements

The authors would like to acknowledge the staff of Gauhati Medical College and Hospital, Guwahati, Assam, India for their support in sample collection during the study.

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Authors and Affiliations

  1. Department of Bioengineering and Technology, Gauhati University, Guwahati, 781 014, India

    Somdatta Das & Diptika Tiwari

  2. Department of Medicine, Gauhati Medical College and Hospital, Guwahati, 781 032, India

    Chitralekha Baruah

  3. Gauhati Neurological and Research Centre, Guwahati, 781 022, India

    Anjan Kumar Saikia

  4. Department of Biotechnology, Gauhati University, Guwahati, 781 022, India

    Sujoy Bose

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  1. Somdatta Das
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  2. Chitralekha Baruah
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  3. Anjan Kumar Saikia
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  4. Diptika Tiwari
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  5. Sujoy Bose
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Correspondence to Sujoy Bose.

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Corresponding editor: Indrajit Nanda

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Das, S., Baruah, C., Saikia, A.K. et al. Genetic and expression changes in \(\hbox {TNF-}\upalpha \) as a risk factor for rheumatoid arthritis pathogenesis in northeast India. J Genet 98, 3 (2019). https://doi.org/10.1007/s12041-018-1054-1

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  • DOI: https://doi.org/10.1007/s12041-018-1054-1

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