The genetics of lupus: a functional perspective

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong genetic component and is characterized by chronic inflammation and the production of anti-nuclear auto-antibodies. In the era of genome-wide association studies (GWASs), elucidating the genetic factors present in SLE has been a very successful endeavor; 28 confirmed disease susceptibility loci have been mapped. In this review, we summarize the current understanding of the genetics of lupus and focus on the strongest associated risk loci found to date (P <1.0 × 10−8). Although these loci account for less than 10% of the genetic heritability and therefore do not account for the bulk of the disease heritability, they do implicate important pathways, which contribute to SLE pathogenesis. Consequently, the main focus of the review is to outline the genetic variants in the known associated loci and then to explore the potential functional consequences of the associated variants. We also highlight the genetic overlap of these loci with other autoimmune diseases, which indicates common pathogenic mechanisms. The importance of developing functional assays will be discussed and each of them will be instrumental in furthering our understanding of these associated variants and loci. Finally, we indicate that performing a larger SLE GWAS and applying a more targeted set of methods, such as the ImmunoChip and next generation sequencing methodology, are important for identifying additional loci and enhancing our understanding of the pathogenesis of SLE.

MicroRNAs in the key events of systemic lupus erythematosus pathogenesis

“…Family studies indicate 66% heritability, and the concordance rate in monozygotic and dizygotic twins is in the range of 24-69% and only 2-5% (ref. 64 ), respectively. although genome-wide association studies (GWas) reliably determine sle risk locations, some genetic predisposing factors may differ between populations.…”

Математическая модель гуморального иммунного ответа для исследования Th17 аутоиммунитета

“…Then two days later a process started of their replacing by IgG synthesizing plasmocytes, thereby after two weeks IgG antibodies began to prevail. It is known that individuals with a low threshold for activation of B lymphocytes are susceptible to autoimmune diseases [39]. Computational experiment with reduced activation threshold leads to a strong immune reaction even in the case of single injection of low dose of antigen.…”

“…Recently genome-wide association studies have identified predisposition to Th17 immune response in patients with systemic lupus erythematosus (which is a severe autoimmune disease) [39]. To examine the role of Th17 in this disease a special extension of the model has been made.…”

CLINICAL SIGNIFICANCE OF SOLUBLE SERUM FAS AND APO1/FAS GENE POLYMORPHISM (RS1800682) -670A>G IN SYSTEMIC LUPUS ERYTHEMATOSUS.

“…The genetic heritability of SLE is approximately 66%. Genome wide association studies have mapped of 28 disease susceptibility loci which account for not more than10% of the genetic heritability (Guerra et al;2012). Certain major histocompatibility complex class II (MHCII) alleles, such as: HLA-DRB* 0301 and DRB1* 1501, are involved in genetic susceptibility to SLE (Fernando et al;.…”