Determination of estrogen receptor alpha gene (ESR1) polymorphism and its relation to systemic lupus erythematosus disease status

Abstract

Background Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with variable clinical manifestations that can affect various organs and tissues. Estrogen is an important element that performs a vital role in the pathology of SLE. It acts on target cells through binding to estrogen receptors (ERs). This study aimed to assess the effect of ER alpha gene polymorphism on SLE disease activity and clinical manifestations. This study included 30 SLE female patients and 20 healthy subjects as controls. ERα gene (pvull and xbal) polymorphisms were genotyped using the real-time polymerase chain reaction (RT-PCR) and correlated with clinical and laboratory manifestations of SLE as well as the activity and severity scores. Results Regarding ERα (rs1 2234693 Pvull) polymorphism, the TC and CC genotypes were mainly associated with SLE patients, with a high frequency of the mutant C allele. The TT genotype was found mainly in the control group. Concerning rs2 9340799 Xbal polymorphisms, the AG, AA, and GG genotypes frequencies were not significantly different between patient and controls. The TC/AA, CC/GG, and CC/GG genotypes were the most prevalent combinations among SLE patients, while the later combination is completely absent from the control group. There was a significant statistical association with the AA genotype with the neurological disorders and/or hematological affection in SLE patients. The TC genotype was more related to serositis, leucopenia and pyuria, while the AA polymorphism was associated only with leucopenia. Conclusions We conclude that the study offers a clue to the associations of ERα gene polymorphisms in SLE disease, and the combinations relevant to certain clinical manifestations. Estrogen level itself does not affect SLE susceptibility or activity but the mutations in its receptors are the main pathogenic factor.

Disease-Associated SNP Variants of Vitamin D Receptor Exhibit Compromised Receptor Function and Genome Bookmarking Properties

“…According to the studies, several gene polymorphisms of NR have been found to be associated with diverse diseases [25][26][27] . Homodimeric receptor ERα harbouring SNPs (rs2234693) is a pathogenic factor for Systemic Lupus Erythematosus (SLE) disease severity 28 . Similarly, polymorphism in other NRs, such as Heterodimeric receptor THR and orphan receptor HNF-4α, are reported in the risk of hypertension/ systolic BP and Crohn's disease, respectively [29][30] .…”