Determination of the association of ETS1 and WDFY4 gene polymorphisms with systemic lupus erythematosus in an Iranian population.



Systemic Lupus Erythematous (SLE) is a relapsingremitting autoimmune disorder which involves many different organs and can be characterized by several immunological abnormalities. These include the presence of hyper-reactive T and B cells and the production of an array of auto-antibodies against serological, intracellular, nucleic acid and cell surface antigens [1, 2]. The prevalence of SLE is approximately 1 in 2,500 Europeans with a sex ratio of 9:1. The disease is more frequent in people with non-European ancestry [2, 3]. Davatchi et al. reported a prevalence of 0.04% for SLE in a WHO-ILAR COPCORD study conducted in Iran.
 Considering the wide range of clinical manifestations and the heterogeneous nature of the SLE phenotype, the American College of Rheumatology (ACR) has defined Eleven clinical criteria to identify patients, namely malar rash, discoid rash, photosensitivity, oral ulcers, non-erosive arthritis, pleuritis, renal disorders, neurologic disorders, hematologic disorders, immunologic disorders and, positive antinuclear antibodies [4].
 Despite the fact that the exact etiology of SLE remains unclear, strong genetic linkage has been well accepted for this disease. Its heritability is estimated to be approximately 66%, with concordance rates of 24% to 57% in monozygotic twins and 2% to 5% in dizygotic twins5 . The role of genetic predisposition is highly attributable to the disease. According to recent studies, SLE is characterized as a polygenic genetic model.

As many as 100 genes could be involved, and every gene may have only a moderate effect size [6-8]. According to recent genome-wide association studies (GWAS), ETS1 and WDFY4 were introduced as novel predisposing genes for SLE [9, 10].

Determination of the association of ETS1 and WDFY4 gene polymorphisms

V-ets avian erythroblastosis virus E26 oncogene homolog 1 (ETS1) is a negative regulator of B-cell differentiation and T helper 17 (Th17) cell proliferation. It has been shown that Patients with SLE present a reduced expression of ETS1, which might contribute to abnormal B-cell differentiation into autoantibody secreting plasma cells and increased number Determination of the association of ETS1 and WDFY4 gene polymorphisms with systemic lupus erythematosus in an Iranian population: Systemic Lupus Erythematosus (SLE) is a heterogeneous complex relapsing-remitting autoimmune disease.

The role of genetics is obvious in predisposition of the disease. Several Single Nucleotide Polymorphisms (SNPs) in ETS1 and WDFY4 showed association with SLE in genome-wide association studies. The aim of this study was to examine the association of the SNPs in ETS1 and WDFY4 genes with SLE in an Iranian population. This study was performed on 280 patients that were not related to one another, and 281 healthy control subjects matched based on age, sex, and ethnicity, all of which were of Iranian origin. Rs10893872 and rs1128334 in the ETS1 gene, and rs877819 and rs707397 in the WDFY4 gene were genotyped using MGB TaqMan Allelic Discrimination Real-Time PCR. Our results showed no association in all mentioned SNPs with the susceptibility and clinical features of SLE in the Iranian population. The results were not consistent with genome-wide association studies performed on Asian and Caucasian populations.