Association of the HLA‐G gene +3142C>G polymorphism with systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease that affects several organs and systems. Its etiology remains unknown, although it is probably multifactorial. The human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility complex I molecule characterized by restricted expression and low DNA polymorphism. HLA-G plays a role in immunosuppression through different mechanisms. In inflammatory diseases, it has been postulated that HLA-G expression may be a possible mechanism of tissue protection against exacerbated inflammatory response. On the 3' untranslated region (3' UTR) of the HLA-G gene, there is an insertion/deletion polymorphism of 14 bp (rs1704) that was shown to influence the mRNA stability. The influence of this polymorphism in disease susceptibility is controversial. Also in the 3' UTR there is a single nucleotide polymorphism C/G (rs1063320) on the position +3142, at a possible binding site for microRNAs (miRNAs) and having an influence on miRNA affinity. In this study, we analyzed the +3142C>G and the 14 bp polymorphisms in 195 SLE European-derived female patients. Our findings show a significant increase of the +3142G allele frequency among patients as compared with controls (0.58 vs 0.47, P = 0.011). Also, patients presented a higher frequency of the GG genotype (OR = 1.90, 95% CI: 1.08-3.42). Double heterozygotes for the two polymorphisms presented a milder mean systemic lupus erythematosus disease activity index (SLEDAI) than heterozygotes for only one of the variants or non-heterozygous individuals (1.56 vs 3.15 and 3.26, respectively, corrected P = 0.044). These results suggest the involvement of the HLA-G molecule on SLE susceptibility and outcome.

SNPs in MicroRNA Binding Sites as Prognostic and Predictive Cancer Biomarkers

“…SNPs within miRNA binding sites have been found to be associated with Parkinson's Disease, 15 rheumatoid arthritis, 16 systemic lupus erythematosus, 17 Crohn's Disease, 18 and psoriasis, 19 among others. Yu et al 20 were one of the first groups to investigate cancer-associated SNPs within miRNA binding sites.…”

HLA-E, HLA-F and HLA-G — The Non-Classical Side of the MHC Cluster

“…Double heterozygotes for the two polymorphisms presented a milder mean systemic lupus erythematosus disease activity index (SLEDAI) than heterozygotes for only one of the variants or non-heterozygous individuals (1.56 vs 3.15 and 3.26, respectively, corrected P = 0.044). These results suggest the involvement of the HLA-G molecule on SLE susceptibility and outcome (Consiglio et al, 2011). The interest of HLA-G in multiple sclerosis (MS) has been growing in the last decade.…”

Relationship between the HLA-G 14bp insertion/deletion polymorphism and susceptibility to autoimmune disease: a meta-analysis

“…In SLE, to date, conflicting results have been reported. Rizzo et al (2008) reported an increased frequency of the 14-bp INS among Italian patients, and Veit et al (2009) and Consiglio et al (2011) reported an excess of heterozygotes in Brazilian patients. However, Wu et al (2009) detected no association between the HLA-G 14-bp INS/DEL polymorphism and SLE among Chinese patients.…”

“…Many studies have investigated the complications of pregnancy, such as recurrent spontaneous abortion and pre-eclampsia. Several studies have suggested that the HLA-G 14-bp INS/DEL polymorphism is associated with AIDs, such as SLE (Rizzo et al, 2008;Veit et al, 2009;Wu et al, 2009;Consiglio et al, 2011), RA Veit et al, 2008), juvenile idiopathic arthritis (Veit et al, 2008), multiple sclerosis (Kroner et al, 2007), ulcerative colitis (Glas et al, 2007), Crohn's disease (Glas et al, 2007), idiopathic dilated cardiomyopathy (Lin et al, 2007), pemphigus vulgaris, and non-segmental vitiligo (Jeong et al, 2014).…”