Centre for Inflammation Research, The University of Edinburgh, Edinburgh, UK.
Reprod Fertil. 2022 Apr 4;3(2):R51-R65. doi: 10.1530/RAF-21-0078. eCollection 2022 Apr 1.
Endometriosis is a chronic neuro-inflammatory disorder the defining feature of which is the growth of tissue (lesions) that resembles the endometrium outside the uterus. Estimates of prevalence quote rates of ~10% of women of reproductive age, equating to at least 190 million women world-wide. Genetic, hormonal and immunological factors have all been proposed as contributing to risk factors associated with the development of lesions. Twin studies report the heritable component of endometriosis as ~50%. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) that appear over-represented in patients with endometriosis, particularly those with more extensive disease (stage III/IV). In different sample populations, there has been replication of SNPs near genes involved in oestrogen and other steroid regulated pathways including (oestrogen receptor alpha), , , and MAPK kinase signalling. Comparisons with GWAS conducted on other patient cohorts have found links with reproductive traits (age at menarche) and disorders (fibroids, endometrial and ovarian cancer) and common co-morbidities (migraine, depression, asthma). In summary, genetic analyses have provided new insights into the hormone-regulated pathways that may contribute to increased risk of developing endometriosis some of which may act in early life. New studies are needed to clarify the relationship between the many SNPs identified, the genes that they regulate and their contribution(s) to development of different forms of endometriosis. We hope that more advanced methods allowing integration between GWAS, epigenetic and tissue expression data will improve risk analysis and reduce diagnositic delay.
Endometriosis is a debilitating reproductive disorder affecting ~10% of reproductive-age women, and those assigned female at birth, which causes a range of symptoms including chronic pain and infertility. The reason why some, but not all these individuals, develop the lesions that characterise the disease are poorly understood, but recently attention has focused on genetic risk factors to explain why the incidence is higher in some families. Studies on large cohorts of patients with comparison of their DNA to women without endometriosis or with other disorders have documented changes in genes associated with steroid hormone production or action. The results provide further evidence that endometriosis shares genetic risk factors with other disorders of the reproductive system and a platform for new ideas related to risk, biomarkers and therapies.
子宫内膜异位症是一种慢性神经炎症性疾病，其特征性表现为子宫内膜组织（病变）在子宫外生长。患病率估计为育龄妇女的 10%左右，相当于全世界至少有 1.9 亿名女性。遗传、激素和免疫因素都被认为是与病变发展相关的危险因素。双胞胎研究报告称，子宫内膜异位症的遗传成分约为 50%。全基因组关联研究（GWAS）已经确定了单核苷酸多态性（SNPs），这些 SNPs 在子宫内膜异位症患者中似乎更为常见，特别是那些疾病更广泛的患者（III/IV 期）。在不同的样本人群中，与雌激素和其他类固醇调节途径相关的基因附近的 SNPs 已经得到了复制，包括 (雌激素受体 alpha)、、、和 MAPK 激酶信号。与对其他患者队列进行的 GWAS 比较发现，与生殖特征（初潮年龄）和疾病（肌瘤、子宫内膜和卵巢癌）以及常见合并症（偏头痛、抑郁、哮喘）有关。总之，遗传分析为激素调节途径提供了新的见解，这些途径可能导致子宫内膜异位症的风险增加，其中一些途径可能在生命早期就起作用。需要新的研究来阐明已识别的许多 SNPs 之间的关系、它们调节的基因以及它们对不同形式子宫内膜异位症的贡献。我们希望更先进的方法，允许 GWAS、表观遗传和组织表达数据之间的整合，将改善风险分析并减少诊断延迟。
子宫内膜异位症是一种影响 10%育龄妇女和出生时被指定为女性的人的致残性生殖疾病，它会引起一系列症状，包括慢性疼痛和不孕。为什么有些人但不是所有人都会发展为疾病特征性的病变，目前还知之甚少，但最近人们的注意力集中在遗传风险因素上，以解释为什么这种疾病在某些家族中的发病率更高。对大量患有该疾病的患者进行的研究，将其 DNA 与没有子宫内膜异位症或患有其他疾病的女性进行了比较，发现了与类固醇激素产生或作用相关的基因变化。这些结果进一步证明了子宫内膜异位症与生殖系统的其他疾病具有遗传风险因素，并为与风险、生物标志物和治疗相关的新想法提供了一个平台。
