The impact of HLA-G, LILRB1 and LILRB2 gene polymorphisms on susceptibility to and severity of endometriosis

Abstract

Endometriosis is a disease in which endometriotic tissue occurs outside the uterus. Its pathogenesis is still unknown. The most widespread hypothesis claims that ectopic endometrium appears as a result of retrograde menstruation and its insufficient elimination by immunocytes. Some reports have shown expression of non-classical HLA-G molecules on ectopic endometrium. HLA-G is recognized by KIR2DL4, LILRB1 and LILRB2 receptors on natural killer (NK) and other cells. These receptors are polymorphic, which may affect their activity. In this study we investigated whether HLA-G, KIR2DL4, LILRB1 and LILRB2 polymorphisms may influence susceptibility to endometriosis and disease progression. We used polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism (PCR-RFLP) and allelic discrimination methods with TaqMan SNP Genotyping Assays for typing of 276 patients with endometriosis and 314 healthy fertile women. The HLA-G rs1632947:GG genotype was associated with protection against the disease and its severe stages; HLA-G rs1233334:CT protected against progression; LILRB1 rs41308748:AA and LILRB2 rs383369:AG predisposed to the disease and its progression. No effect of KIR2DL4 polymorphism was observed. These results support the role of polymorphisms of HLA-G and its receptors LILRB1 and LILRB2 in susceptibility to endometriosis and its progression.Electronic supplementary materialThe online version of this article (10.1007/s00438-017-1404-3) contains supplementary material, which is available to authorized users.

Association of Soluble HLA-G Plasma Level and HLA-G Genetic Polymorphism With Pregnancy Outcome of Patients Undergoing in vitro Fertilization Embryo Transfer

“…Secretion of sHLA-G in plasma from A-C-ins women also differed from those carrying G-C-ins when embryo transfer resulted in pregnancy (p = 0.016; median, 74.56 vs. 37.21 IU/ml; Figure 3A, Supplementary Table 2) and in a miscarriage (p = 0.013; median, 71.83 vs. 46.76; Figure 3C, Supplementary Table 4). Similar observations were obtained for A-C-del vs. G-C-ins carriers in pregnancy (p = 0.04; median, 58.95 vs. 37.21 IU/ml; Figure 3A, Supplementary Table 2) and in a miscarriage (p = 0.05; median, 64.10 vs. 46.76 IU/ml; Figure 3C, Supplementary Table 4). Less significant differences (p ∼ 0.05) were found also for A-G-del, G-T-ins vs. G-C-ins haplotypes comparisons.…”

Genes’ Interactions: A Major Contributor to the Malignant Transformation of Endometriosis

“…Interestingly, a recent case report [48] described the rare case of a patient with endometriosis and a long history of non-gynecological comorbidities, including autoimmune diseases such multiple sclerosis and Crohn’s disease. This case seems to confirm the findings of Fung et al The effect of SNPs on the progression of and development of endometriosis was also confirmed by a recent study [49] showing that these events control the disease.…”

Defining the genetic profile of endometriosis (Review)

“…This can also be expressed by the ectopic endometrium in the peritoneal cavity, thus being recognized by cells of the immune system, through the receptors LILRB1 and LILRB2. By performing genotype assays in a total of 590 individuals, researchers have deduced that genotypes LILRB1 rs41308748 AA and LILRB2 rs383369 AG, as well as the HLA-G rs1632947 GG and HLA-G rs1233334 CT are regulators of disease progression and susceptibility (114).…”