Laboratório de Pesquisa de Ciências Farmacêuticas, Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste, Rio de Janeiro, RJ, Brazil; Programa de Pós-guaduação em Saúde Pública e Meio Ambiente, Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
Grupo de Oncologia Molecular -CI, Instituto Português de Oncologia, Porto, Portugal.
Exp Mol Pathol. 2021 Apr;119:104616. doi: 10.1016/j.yexmp.2021.104616. Epub 2021 Jan 31.
DROSHA and DICER1 enzymes participate in the main stages of microRNA synthesis. Polymorphisms can influence mRNAs stability and genes expression, and hence affect the binding of miRNAs. Thus, the present study evaluated the association of DROSHA and DICER1 polymorphisms in the development of endometriosis and other diseases.
A total of 240 endometriosis cases and 242 controls were genotyped for the DROSHA rs10719 G > A and DICER1 rs3742330 A > G polymorphisms using the TaqMan system. The association between polymorphisms and endometriosis was estimated by binary logistic regression. A literature review was also performed including all published articles (PubMed database) until December 2020, regarding the association of the studied polymorphisms and different diseases.
DICER1 rs3742330GG was only found in endometriosis cases (2.1%) and deep infiltrative endometriosis (DIE) (2.5%). The DICER1 rs3742330GG genotype was significantly associated with endometriosis (P < 0.05), suggesting a tendency to present an increased risk for disease. DROSHA rs10719A and DICER1 rs3742330G allele frequencies varied among populations (6%-79% and 10.2%-55.1%, respectively). In the Brazilian population, the frequencies of these alleles were 42.3% and 7.3%, respectively. Both polymorphisms were risk factors for nonsyndromic orofacial clefts, tuberculosis, stroke ischemia and mortality after stroke, recurrent idiopathic pregnancy loss, and some types of cancer. Moreover, the DICER1 rs3742330 polymorphism was a protective factor for precancerous cervical lesions, different types of cancer and tuberculosis.
The results suggest that only the DICER1 rs3742330 A > G polymorphism may be associated with susceptibility to endometriosis. The frequencies of both polymorphisms were significantly different among populations, and there were discrepancies in the risk associations with the development of diseases.
DROSHA 和 DICER1 酶参与 microRNA 合成的主要阶段。多态性可以影响 mRNA 的稳定性和基因表达，从而影响 miRNAs 的结合。因此，本研究评估了 DROSHA 和 DICER1 多态性与子宫内膜异位症及其他疾病发展的关系。
采用 TaqMan 系统对 240 例子宫内膜异位症病例和 242 例对照者的 DROSHA rs10719 G>A 和 DICER1 rs3742330 A>G 多态性进行基因分型。采用二元逻辑回归估计多态性与子宫内膜异位症的关系。还进行了文献综述，包括截至 2020 年 12 月在 PubMed 数据库中发表的所有关于研究多态性与不同疾病关系的文章。
DICER1 rs3742330 GG 仅在子宫内膜异位症病例（2.1%）和深部浸润性子宫内膜异位症（DIE）（2.5%）中发现。DICER1 rs3742330 GG 基因型与子宫内膜异位症显著相关（P<0.05），提示疾病发生风险增加的趋势。DROSHA rs10719A 和 DICER1 rs3742330G 等位基因频率在不同人群中存在差异（分别为 6%-79%和 10.2%-55.1%）。在巴西人群中，这些等位基因的频率分别为 42.3%和 7.3%。这两种多态性都是非综合征性或面裂、结核病、中风缺血和中风后死亡率、复发性特发性妊娠丢失以及某些类型癌症的危险因素。此外，DICER1 rs3742330 多态性是癌前宫颈病变、不同类型癌症和结核病的保护因素。
结果表明，只有 DICER1 rs3742330 A>G 多态性可能与子宫内膜异位症的易感性有关。两种多态性在不同人群中的频率有显著差异，与疾病发展的风险关联也存在差异。
