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

Aleksandra Bylińska,Jacek R Wilczyński,Andrzej Wiśniewski,Rafał Płoski,Andrzej Malinowski,Piotr Kuśnierczyk,Monika Jasek,Łukasz Milewski,Ewa Barcz,Paweł Radwan,Marta Wagner,Izabela Nowak,Karolina Wilczyńska,Piotr Roszkowski,Michał Radwan,Paweł Kamiński,Wanda Niepiekło-Miniewska,Jacek Malejczyk

doi:10.1007/s00438-017-1404-3

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.

Highlights

Endometriosis is an estrogen-dependent gynecological disease, affecting about 10% of women in reproductive age
We found lower representation of rs1632947:GG genotype in patients with endometriosis than in controls (P = 0.04, Pcorr. = 0.12, odds ratio (OR) = 0.61, 95% CI = 0.39–0.96; Table 2)
Comparison of patients with minimal and mild (I + II) with moderate and severe (III + IV) endometriosis revealed a protective effect of rs1632947:GG genotype (P = 0.04, OR = 0.2, 95% CI = 0.04–0.97), and, in addition, of rs1233334:CT genotype (P = 0.04, OR = 0.09, 95% CI = 0.01–0.62; Table 3)

Summary

Introduction

Endometriosis is an estrogen-dependent gynecological disease, affecting about 10% of women in reproductive age. It is associated with the occurrence of endometrium outside. Extended author information available on the last page of the article the uterus. One hypothesis of endometriosis development is Sampson’s theory of retrograde menstruation (Sampson 1927; Dastur et al 2010). According to this theory, retrograde menstruation may result in implantation, survival and growth of endometrial cell foci in the peritoneal cavity. Women with endometriosis were found to have reduced activity of natural killer (NK) cells

Methods

Results

Conclusion