Uncorrected Proof Gene Cell Tissue. In Press(In Press):e115542. Published online 2022 May 15. doi: 10.5812/gct-115542. Research Article Association Study of TNF-α -308 G/A (rs1800629) and -863 C/A (rs1800630) Polymorphisms with Systemic Lupus Erythematosus in the Iranian Lor Population Zeynab Mashayekh 1 , Mahsa Rafieian 1 and Seyed Reza Kazeminezhad 1, * 1 Department of Biology, Section of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran * Corresponding author: Department of Biology, Section of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran Email: kazemi_reza@scu.ac.ir Received 2021 May 25; Revised 2022 February 06; Accepted 2022 February 08. Abstract Background: Systemic lupus erythematosus (SLE) is caused by a combination of environmental and genetic factors; studying the association between regulatory genes and this disease may determine the genetic causes of interfering with SLE. In different popu- lations, studies have shown that the tumor necrosis factor α (TNF-α) gene (as a candidate gene) can contribute to the formation and progression of lupus disease. Objectives: This study aimed to indicate the possible association between the increased rate of SLE hazard and 2 single-nucleotide polymorphisms (SNPs) of rs1800629 and rs1800630 genetic polymorphisms in the TNF-α promoter gene in the Lor population. Methods: According to the American College of Rheumatology (ACR) criteria, 120 unrelated SLE patients and 120 healthy controls with no family or personal history of autoimmune diseases were selected. DNA was genotyped for the TNF-α promoter (-308 G/A and -863 C/A) by the tetra-primer amplification-refractory mutation system (tetra-primer ARMS)–polymerase chain reaction (PCR) method. Results: The frequency difference between allele A (mutant allele) and allele C (normal allele) at position -863 of the TNF-α promoter gene (odds ratio [OR] = 3.426; 95% CI, 1.985 - 5.914) was notably higher in SLE patients than in control subjects. Also, a significant relation was obtained among the rs1800830 AA genotype and increased risk of SLE (OR = 4.489; 95% CI, 2.464 - 8.177; P < 0.0001). Our results for rs1800629 at position -308 were not remarkably different. Conclusions: We found a significant correlation between allelic and genotype frequencies between rs1800830 (-863 C/A) TNF-α SNP and SLE in our study. However, no significant correlation was observed between the rs1800629 (-308 G/A) TNF-α promoter and the increase of SLE hazard in the Lor population. No remarkable association was obtained between TNF-α gene rs1800629 (-308 G/A) and rs1800630 (-863 C/A) SNPs and anti-double-stranded DNA (anti-dsDNA) or antinuclear antibody (ANA), which are some of the symptoms of SLE. Keywords: Systemic Lupus Erythematosus, TNF-α, Single-nucleotide Polymorphism, rs1800629, rs1800630 1. Background Systemic lupus erythematosus (SLE) is one of the com- plex diseases with a wide range of clinical criteria, includ- ing antinuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibodies (1-3). The incidence of SLE dis- ease varies between different populations. The cause of SLE disease is unknown. Environmental and genetic fac- tors are among the risk factors for SLE. The prevalence of SLE is high in Asians and notably in Iranian populations (4, 5). Recently, many efforts have been made to find a link between SLE susceptibility and genetic variants (6-9). The tumor necrosis factor α (TNF-α) gene produces an in- ducible pro-inflammatory cytokine (10, 11), which is fixed in human chromosome 6 within the major histocompat- ibility complex (MHC) class III region (12). It seems that the TNF-α gene is connected to the pathogenesis of inflam- matory disorders (13, 14). Several studies on different dis- eases have shown the effect of single-nucleotide polymor- phisms (SNPs) on the TNF-α promoter region (15, 16). How- ever, studies have not definitely determined the associa- tion between TNF-α promoter gene SNPs and SLE (17-20). Rs18008629 at position -308 G/A polymorphism is related to increased potential and intensity in a variety of autoim- mune diseases (19, 21-23). The second polymorphism, a common functional polymorphism is located at position -863 C/A (24). Several studies have analyzed the association between rs1800630 at the position -863 C/A TNF-α promoter Copyright © 2022, Gene, Cell and Tissue. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.