【摘要】 目的通过人群研究和SNP功能分析,探讨对氧磷酶1(PON1)基因3’UTR区SNPs对miRNA结合的影响,为铅中毒对心血管系统产生危害的机制提供新的思路。方法 ELISA方法检测铅中毒组和对照组中血清PON1含量,分析其在不同血铅浓度人群中的变化情况;Taqman MGB探针检测PON1基因rs854550和rs854552基因型分布情况;荧光素酶双报告基因法检测has-miR-218与rs854552所在区域结合情况。结果低浓度血铅值的个体PON1血清水平显著下降(P<0.05);rs854550和rs854552多态性位点在铅中毒组和对照组中未发现显著差异;报告基因实验也未能发现has-miR-218可能受rs854552影响其与3’UTR结合。结论铅暴露能引起人体PON1表达改变,但本研究尚不能证明PON1基因3’UTR区多态性在铅中毒所致心血管疾病中的作用,需进一步实验寻找相关易感SNP,为明确铅中毒分子机制提供依据。更多还原

【Abstract】 Objective To detect the association between SNPs in 3’UTR of PON1 and miRNA by analyzing population data and function of SNP,and provide a new direction of the mechanism of lead poisoning on the cardiovascular system. Methods Serum PON1 levels were detected in lead poisoning population and control population by ELISA; genotypes distribution of rs854550 and rs854552 were detected by Taqman MGB; association between has-miR-218 and rs854552 were detected by Luciferase reporter gene assay. Results Individuals with low blood lead level had a significant decrease in serum PON1 level(P <0. 05),no significant difference between lead poisoning and control group was found in rs854550 and rs854552 genotypes,and no influence from rs854552 in the combination of has-miR-218 and 3’UTR. Conclusion Lead exposure can change PON1 level,however,it is not yet clear whether SNPs in 3’UTR of PON1 gene play a role in lead poisoning. Further studies are needed to find related susceptible SNPs,and to provide new evidence for the mechanisms of lead poisoning.更多还原