Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, QLD, Australia.
Institute for Molecular Bioscience, The University of Queensland, Brisbane, 4072, QLD, Australia.
Best Pract Res Clin Obstet Gynaecol. 2018 Jul;50:61-71. doi: 10.1016/j.bpobgyn.2018.01.012. Epub 2018 Feb 8.
Developments in high-throughput genotyping technology have driven discovery of genomic regions associated with an increased risk of endometriosis. In all, 16 genomic regions have been associated with risk of endometriosis in one or more populations. The latest meta-analysis including 17,045 endometriosis cases identified 14 genomic regions supported by results from multiple studies. No independent associations were identified from direct genotyping of common and low-frequency protein-coding variants. This suggests that the most common genetic factors that contribute to endometriosis risk are located in regulatory DNA sequences and alter the regulation of gene transcription. Evidence from different methods is essential to identify the target genes and transcripts that contribute to altered disease risk. Potential target genes in three chromosome regions showing altered gene regulation include LINC00339 and CDC42 on chromosome 1, CDKN2A-AS1 on chromosome 9, and VEZT on chromosome 12. Further functional studies are needed to confirm the causal genes in these and other regions to understand pathways that increase endometriosis risk and help identify novel targets for interventions to improve diagnosis and treatment.
高通量基因分型技术的发展推动了与子宫内膜异位症风险增加相关的基因组区域的发现。总共有 16 个基因组区域在一个或多个人群中与子宫内膜异位症风险相关。最新的荟萃分析包括 17045 例子宫内膜异位症病例，确定了 14 个得到多项研究结果支持的基因组区域。从常见和低频蛋白编码变异的直接基因分型中未发现独立关联。这表明，导致子宫内膜异位症风险的最常见遗传因素位于调节 DNA 序列中，并改变基因转录的调节。来自不同方法的证据对于确定导致疾病风险改变的靶基因和转录本至关重要。三个染色体区域显示基因调控改变的潜在靶基因包括染色体 1 上的 LINC00339 和 CDC42、染色体 9 上的 CDKN2A-AS1 和染色体 12 上的 VEZT。需要进一步的功能研究来确认这些和其他区域中的因果基因，以了解增加子宫内膜异位症风险的途径，并帮助确定改善诊断和治疗的新干预目标。
