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

Autor: Somdatta Das, Anjan Kumar Saikia, Diptika Tiwari, Sujoy Bose, Chitralekha Baruah
Rok vydání: 2019
Předmět:
Zdroj: Journal of Genetics. 98
ISSN: 0973-7731
0022-1333
DOI: 10.1007/s12041-018-1054-1
Popis: 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.
Databáze: OpenAIRE
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