Gajbhiye Rahul, McKinnon Brett, Mortlock Sally, Mueller Michael, Montgomery Grant
1 Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD, Australia.
3 Department of Clinical Research, ICMR-National Institute for Research in Reproductive Health, Parel, Mumbai, Maharashtra, India.
Reprod Sci. 2018 Sep;25(9):1307-1317. doi: 10.1177/1933719118768688. Epub 2018 Apr 18.
Endometriosis is characterized by the growth of epithelial and stromal cells outside the uterine cavity. It has a complex etiology and affects ∼10% of reproductive age women. It is accompanied by a chronic inflammatory response with substantial evidence to indicate genetic susceptibility. The causal genes and their pathways leading to endometriosis, however, are still unknown. Recently, genomewide association studies on endometriosis identified 14 genomic risk loci in women of European and Japanese ancestry. It is becoming increasingly clear that these risk regions are intergenic and thus contribute to disease susceptibility through regulatory mechanisms, most likely mediated through regulation of genes within a restricted distance from the risk variants. One endometriosis risk locus has been detected at chromosome 2q13 within an inflammatory-rich region of gene transcripts and thus may play a role in the inflammation component of the disease. We carried out detailed analysis of the genomic region 250 kb on either side of sentinel SNP rs10167914 and identified 21 transcripts which contained 6 interleukin (IL)-1 family genes, 3 previously reported coding genes that have a relationship to inflammation, 4 novel coding, or pseudogenes, and 8 noncoding RNA transcripts. Through an extensive literature search, we examined the roles these genes and their resultant proteins play in endometriosis pathogenesis. The results suggest alteration in the expression the IL-1 family transcripts either alone or as a complex milieu could have a significant influence on endometriosis and should be prioritized for future study on the implications of inflammation on endometriotic lesions.
子宫内膜异位症的特征是子宫腔外上皮细胞和间质细胞的生长。其病因复杂，影响约10%的育龄妇女。它伴有慢性炎症反应，有大量证据表明存在遗传易感性。然而，导致子宫内膜异位症的致病基因及其途径仍不清楚。最近，针对子宫内膜异位症的全基因组关联研究在欧洲和日本血统的女性中确定了14个基因组风险位点。越来越清楚的是，这些风险区域位于基因间，因此通过调控机制导致疾病易感性，最有可能是通过调控与风险变异距离有限的基因来实现。在2号染色体q13的一个富含炎症基因转录本的区域检测到一个子宫内膜异位症风险位点，因此可能在该疾病的炎症成分中起作用。我们对前哨单核苷酸多态性rs10167914两侧各250 kb的基因组区域进行了详细分析，确定了21个转录本，其中包含6个白细胞介素（IL）-1家族基因、3个先前报道的与炎症相关的编码基因、4个新的编码基因或假基因以及8个非编码RNA转录本。通过广泛的文献检索，我们研究了这些基因及其产生的蛋白质在子宫内膜异位症发病机制中的作用。结果表明，IL-1家族转录本单独或作为复杂环境的表达改变可能对子宫内膜异位症有重大影响，应优先用于未来关于炎症对子宫内膜异位病变影响的研究。
