Genetic factors involved in the co‑occurrence of endometriosis with ankylosing spondylitis (Review)

Abstract

Previous research has revealed an association between endometriosis and various autoimmune diseases, while recent data suggest, for the first time, an association between endometriosis and the risk of developing ankylosing spondylitis (AS). AS, the prototype of spondyloarthritides diseases, is a systemic, chronic, immune-mediated inflammatory arthritis, which primarily affects the spine and sacroiliac joints, as well as the axial skeleton with or without extraspinal manifestations. AS is of polygenic inheritance and numerous immunologically relevant genes contribute to its development. Endometriosis is an enigmatic, relatively common, benign, estrogen-dependent, heterogeneous gynecological disease, influenced by multiple genetic, epigenetic and environmental factors. It is characterized by the growth of endometrial tissue occurring in sites other than the uterine cavity, most commonly in the pelvic cavity, including the ovaries and the uterosacral ligaments, affecting up to 10% of the female population of childbearing age, causing pain and infertility. The present review discusses whether a partially shared genetic background may explain the co-occurrence of these disorders, as well as potential similarities regarding the underlying pathogenetic mechanisms and specific molecular and cellular pathways.

Association of endometriosis with Sjögren's syndrome: Genetic insights (Review)

“…The angiogenic properties of the endometrium and its strong potential to attract blood vessels from the surrounding tissue is well established ( 103 ). Moreover, various potent angiogenic factors such as TGF-α, TGF-β, basic fibroblast growth factor and angiopoietin ( 32 ) have been found to be altered in endometriosis, thus suggesting the involvement of angiogenesis in the ectopic implantation of the endometrial cells ( 104 ). A number of genetic polymorphisms of key components of the angiogenesis mechanism, including placental growth factor rs2268614, hypoxia inducible factor-1α ( HIF-1a ) rs11549465 and vascular endothelial growth factor (VEGF) receptor 1 ( VEGFR1 ) rs9582036, were found to be associated with the development of endometriosis.…”

“…Most importantly, epidemiological studies demonstrated that patients with endometriosis were associated with an increased risk of developing a number of autoimmune diseases compared with unaffected controls due to notable changes in immune-related parameters. The autoimmune diseases included in this category include rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), ulcerative colitis, crohn's disease, coeliac disease, ankylosing spondylitis and autoimmune thyroid disorder (29)(30)(31)(32)(33). however, it is unclear whether autoimmune diseases represent a risk factor of endometriosis, or these two types of diseases share similar pathogenetic mediators.…”

“…Endometriosis is a highly complex disease with numerous genetic, epigenetic and environmental factors interacting with each other, thus contributing to its pathogenesis (15). The identification and functional analysis of the numerous genetic factors involved in the development of endometriosis have notably contributed to the better understanding of the biological processes and molecular mechanisms leading to the disease, as presented in detail in recent studies by our research group (27,30,32). In brief, the strong genetic predisposition of the disease was documented firstly in monozygotic twin-based and family studies (37,38), followed by linkage analysis, various candidate and gene association, genome wide association studies (GwAS), meta-analyses and next-generation sequencing studies (39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53).…”