miRNA成熟相关基因DICER、DROSHA、RAN基因多态性与不明原因复发流产的相关性研究

The Association Between the Polymorphisms of miRNA Biogenesis Related Genes (DICER,DROSHA and RAN) and Unexplained Recurrent Spontaneous Abortion in Chinese Women

目的探讨miRNA成熟关键基因DICER、DROSHA和RAN的基因多态性与女性复发流产的相关性。方法收集2013年6月至2015年12月于四川大学华西第二医院就诊的不明原因复发流产(URSA)患者共217例,至少有1次生育史的育龄妇女为正常对照组390例,对照组为同期进行体检和孕前检查育龄妇女。采用病例对照研究的方法,应用PCR-限制性片段长度多态性技术检测miRNA成熟过程中关键基因DICER rs3742330、DROSHArs10719和RAN rs14035单核苷酸多态性。结果 DICERrs3742330,DROSHArs10719和RANrs14035各等位基因和基因型频率在URSA组和对照组差异无统计学意义(P>0.05)。联合分析发现,DICERrs3742330/DROSHArs10719GG/TT+TC协同会增加复发流产的风险(OR=1.657,95%CI=1.006~2.731,P=0.047)。虽然DICERrs3742330/RANrs14035GG/TT+TC在URSA组较对照组增高,但差异无统计学意义(OR=1.977,95%CI=0.956~4.087,P=0.066),而DROSHA10719/RAN14035TT+TC/TT+TC与复发流产无相关性(OR=0.958,95%CI=0.679~1.353,P=0.808)。结论DICERrs3742330联合DROSHA rs10719可能与URSA相关。

Objective To explore the association between polymorphisms of miRNA biogenesis related gene DICER, DROSHA, RAN and unexplained recurrent spontaneous abortion （URSA） in Chinese women. Methods We recruited 217 patients with URSA （URSA group） and 390 healthy controls who were fertile women with history of more than one successful pregnancy outcome （control group） from June 2013 to December 2015 in the West China Second University Hospital of Sichuan University. The control group was recruited from regular physical examination and prepregnancy check for women of childbearing age during the same period. A case-control study was performed to analyze polymorphism of miRNA machinery genes, including DICER rs3742330, DROSHA rs10719, RAN rs14035, by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. Results The frequencies of genotypes and alleles of DICER rs3742330, DROSHA rs10719, and RAN rs14035 showed no difference between URSA patients and control group （all P〉0.05）. DICER rs3742330/DROSHA rs10719 GG/TC＋TT combinations were synergistically associated with increased URSA risk 〔odds ratio （OR）=1.657, 95% confidence interval （CI）=1.006-2.731, P=0.047〕. Although DICER rs3742330/RAN rs14035 GG / TT＋TC combinations was significantly higher in the URSA group than in the control group, there was no statistical significance （OR=1.977, 95%CI=0.956-4.087, P=0.066）. However, DROSHA10719/RAN14035 TT＋TC/TT＋TC had no significant correlation with URSA （OR=0.958, 95%CI=0.679-1.353, P=0.808）. Conclusion Our study demonstrated the relationship between URSA development and combined genotype.