THU0230 TNF-αLPHA PROMOTER POLYMORPHISMS (G-308A AND G-238A) ARE ASSOCIATED WITH SUSCEPTIBILITY TO SLE: A HOSPITAL-BASED CASE-CONTROL INVESTIGATION
Authors: MOHAPATRA DEBASISH, Rina Tripathy, Aditya Kumar Panda, Manoj Kumar Parida, Saumya Ranjan Tripathy, Bidyut Kumar Das
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Tumour necrosis factor-α (TNF-α) is a proinflammatory cytokine associated with various autoimmune disorders<sup>1</sup>. High levels of TNF-α has been reported in systemic lupus erythematosus (SLE)<sup>2</sup>. Two functional common polymorphisms (G-238A and G-308A) at promoter region of TNF-α gene have been linked to SLE susceptibility in different populations<sup>3,4</sup>. <h3>Objectives:</h3> To investigate association of TNF-α (G-238A and G-308A) polymorphisms with susceptibility/resistance to SLE. <h3>Methods:</h3> A total of 102 female SLE patients and 112 age and sex matched healthy controls were enrolled in the study. Patients were examined in detail, physical findings recorded and SLEDAI 2K calculated to assess disease severity. TNF-α polymorphisms (G-238A &amp; G-308A) were typed by polymerase chain reaction and restriction length polymorphism (PCR-RFLP). Plasma level of TNF-α was quantified by ELISA. Statistical analysis was carried out using GRAPH PAD PRISM -7.01. <h3>Results:</h3> Mean age of SLE patients and healthy controls was 27.84±8.83 and 29.56±5.48 years, respectively. At the time of enrolment, mean disease duration of patients was 2.07±1.13 years. The mean SLEDAI 2K of patients was 16.07±7.66. The prevalence of heterozygous mutant and minor allele of TNF-α (G-238A) polymorphisms were significantly higher in SLE patients compared to healthy controls (GA: P=0.04, OR=2.16; A: P=0.02, OR: 2.09). Furthermore, heterozygous (GA) and minor allele (A) of TNF-α (G-238A) polymorphism were associated with susceptibility to lupus nephritis (GA: P=0.02, OR=2.89; A: P=0.001, OR: 2.92). SLE patients displayed higher levels of plasma TNF-α compared to healthy controls. Although the prevalence of heterozygous mutant and minor allele of TNF-α (G-308A) polymorphism was higher in SLE patients, it was not statistically significant. TNF-α (G-238A and G-308A) variants were associated with higher plasma TNF-α in both SLE patients and healthy control. However, no significant association was observed on distribution of TNF-α polymorphisms (G-238A and G-308A) with severity of disease activity of SLE patients. <h3>Conclusion:</h3> The results of the present study demonstrate that TNF-α (G-238A) variant is associated with higher plasma TNF-α level and increased susceptibility to development of SLE and lupus nephritis. <h3>References:</h3> [1] Aggarwal BB, Gupta SC, Kim JH. Historical perspectives on tumor necrosis factor and its superfamily: 25 years later, a golden journey. Blood. 2012;119(3):651–665. [2] Studnicka-Benke A, Steiner G, Petera P, Smolen JS. Tumour necrosis factor alpha and its soluble receptors parallel clinical disease and autoimmune activity in systemic lupus erythematosus. Br J Rheumatol. 1996;35(11):1067–1074. [3] D'Alfonso S, Colombo G, Della Bella S, Scorza R, Momigliano-Richiardi P. Association between polymorphisms in the TNF region and systemic lupus erythematosus in the Italian population. Tissue Antigens1996;47(6):551–555. [4] Lee YH, Harley JB, Nath SK. Meta-analysis of TNF-alpha promoter−308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet. 2006;14:364–371. <h3>Disclosure of Interests:</h3> None declared