miR-138 rs139365823多态性与先天性心脏病风险的相关性研究

Correlation between Rs139365823 polymorphism in miR-138 and the risk of congenital heart disease

目的探讨miR-138中的遗传多态性是否可能导致先天性心脏病(CHD)的发生和潜在的机制。方法本研究通过miR-138基因分型的方法对100例法洛四联症(TOF)患者及正常对照人群进行病例对照研究。鉴定2个miR-138 SNPs,包括位于pre-miR-138序列中的rs139365823和位于pri-miR-138序列中的rs76987351。结果rs139365823等位基因A的基因型及等位基因频率与TOF风险增加明显相关,但与rs76987351 A/G等位基因无明显相关。PCR数据显示,rs139365823等位基因A明显增加miR-138的表达,而rs76987351等位基因A具有相反的作用。由于TOF是由流出道(OFT)发育异常引起,因此将参与OFT发育有关的Dvl2鉴定为miR-138的直接靶基因。此外,rs139365823等位基因A增强了miR-138对Dvl2的抑制作用。结论本研究证明了miR-138 rs139365823等位基因A增加了miR-138的表达及它对靶基因的抑制作用。

Objective To explore whether a genetic polymorphism in miR-138 may result in the occurrence of congenital heart disease(CHD)and the potential mechanism.Methods A case-control study was performed in 100 patients with tetralogy of Fallot(TOF)and 100 healthy subjects by genotyping miR-138.Two SNPs,including rare rs139365823 located in the pre-miR-138 sequence and rs76987351 located in the pri-miR-138 sequence,were identified by sequencing miR-138.Results The results demonstrated that the genotypes and allele frequencies of the rs139365823 minor allele A were significantly associated with the increased risk of TOF,however,which were not correlated with the rs76987351A/G allele.Real-time PCR data showed that the rs139365823 minor allele A significantly increased the expression of mature miR-138,whereas the rs76987351 minor allele A had the opposite effects.As TOF was caused by severe outflow tract(OFT)abnormal development,the related Dvl2 was regarded as direct target gene of miR-138.In addition rs139365823 minor allele A enhanced the inhibitory efects of miR-138 on Dvl2.Conclusion The miR-138 rs139365823 allele A increases the expression of miR-138 and its inhibitory effect on target genes.