Research Laboratory of Pharmaceutical Sciences, State University Centre of the West Zone, Rio de Janeiro, Brazil; Program of Post-graduation in Public Health and Environment, National School of Public Health, Oswald Cruz Foundation, Rio de Janeiro, RJ, Brazil.
Research Laboratory of Pharmaceutical Sciences, State University Centre of the West Zone, Rio de Janeiro, Brazil; Program of Post-graduation in Public Health and Environment, National School of Public Health, Oswald Cruz Foundation, Rio de Janeiro, RJ, Brazil.
Eur J Obstet Gynecol Reprod Biol. 2020 Dec;255:74-82. doi: 10.1016/j.ejogrb.2020.10.017. Epub 2020 Oct 12.
Endometriosis is a complex and heterogeneous disease in which extrinsic and intrinsic factors, such as genetics, provide to the disease development. Genome-wide association (GWA) studies may be essential to recognize genetic variants associated with the endometriosis risk. However, in the current literature there are some conflicting results between these studies. The aim of the present study was to undertake a systematic review about endometriosis GWA studies, to describe the disease-associated genes and single nucleotide polymorphisms (SNPs) to try to understand the endometriosis etiopathogenesis, besides to discuss possible bias of conflicting results among these studies. This study is a systematic review of GWA studies in endometriosis published until December 31, 2019 by PubMed database, considering the following descriptors: endometriosis and ("polymorphism" or "SNP" or "genetic polymorphism" or "variants" or "locus") and ("GWA" or "Genome-wide" or "Genome wide" or "Genetic association study"). The included studies were analyzed with methodological rigor (STROBE and PRISMA) to enable better quality of case-control and meta-analysis studies, respectively. Of the 88 articles found, only 15 were eligible. All articles had appropriate quality evaluated by STROBE and PRISMA checklists (77% and 81%, respectively). Overall, 35,022 endometriosis cases and 181,760 controls were analyzed. The number of participants in each study was quite different (171 to 17,045 for the cases and 308 to 150,021 for the controls), with a predominance of European ethnicity. Most endometriosis cases (86%) were diagnosed by surgery, while selection of the control group was different among studies. About 47% performed only one stage (discovery stage) and 53% performed both the discovery and replication analyses. Eleven genes/SNPs were associated with endometriosis risk in more than one article (chromosome 1, 2, 6, 7, 9 and 12; WNT4, GREB1, FN1, IL1A, ETAA1, RND3, ID4, NFE2L3, CDKN2B-AS1 and VEZT). SNPs were localized in intergenic and intronic regions, their risk allele frequencies varied among the studies and their results were conflicting. In summary, WNT4 rs7521902, GREB1 rs13394619, FN1 rs1250248, IL1A rs6542095 and VEZT rs10859871 variants are highlighted due to high frequency and pathways and function that each gene influences in the development of endometriosis. However, the replication and validation of these variants in different populations are necessary for a better understanding of the endometriosis etiopathogenesis, in order to optimize the diagnosis and improve the efficiency of clinical treatment of the disease.
子宫内膜异位症是一种复杂且异质的疾病，外在和内在因素（如遗传学）为其发展提供了条件。全基因组关联（GWA）研究对于识别与子宫内膜异位症风险相关的遗传变异可能至关重要。然而，在当前的文献中，这些研究之间存在一些相互矛盾的结果。本研究旨在对子宫内膜异位症的 GWA 研究进行系统评价，描述与疾病相关的基因和单核苷酸多态性（SNP），以试图了解子宫内膜异位症的病因发病机制，并讨论这些研究之间可能存在的矛盾结果的偏倚。本研究是对截至 2019 年 12 月 31 日在 PubMed 数据库中发表的子宫内膜异位症 GWA 研究进行的系统评价，考虑了以下描述符：子宫内膜异位症和（“多态性”或“SNP”或“遗传多态性”或“变体”或“基因座”）和（“GWA”或“全基因组”或“基因组宽”或“遗传关联研究”）。对纳入的研究进行了严格的方法学分析（STROBE 和 PRISMA），以分别为病例对照研究和荟萃分析提供更好的质量。在 88 篇文章中，只有 15 篇符合条件。所有文章均通过 STROBE 和 PRISMA 检查表进行了适当的质量评估（分别为 77%和 81%）。总体而言，分析了 35022 例子宫内膜异位症病例和 181760 例对照。每个研究的参与者数量差异很大（病例为 171 至 17045 例，对照为 308 至 150021 例），以欧洲血统为主。大多数子宫内膜异位症病例（86%）通过手术诊断，而对照组的选择在不同的研究中有所不同。约 47%仅进行了一个阶段（发现阶段），53%进行了发现和复制分析。有 11 个基因/SNP 在超过一篇文章中与子宫内膜异位症风险相关（染色体 1、2、6、7、9 和 12；WNT4、GREB1、FN1、IL1A、ETAA1、RND3、ID4、NFE2L3、CDKN2B-AS1 和 VEZT）。SNP 定位于基因间和内含子区域，其风险等位基因频率在研究之间存在差异，且结果相互矛盾。总之，WNT4 rs7521902、GREB1 rs13394619、FN1 rs1250248、IL1A rs6542095 和 VEZT rs10859871 变体由于其高频率以及每个基因在子宫内膜异位症发展过程中影响的途径和功能而受到关注。然而，为了更好地了解子宫内膜异位症的病因发病机制，需要在不同人群中对这些变体进行复制和验证，以便优化诊断并提高疾病的临床治疗效果。
