Association Study of TNF-α -308 G/A (rs1800629) and -863 C/A (rs1800630) Polymorphisms with Systemic Lupus Erythematosus in the Iranian Lor Population

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 populations, 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.