【摘要】 目的本项目拟探索位9p21.3的非编码RNA(LncRNA ANRIL)拷贝数变异(copy-numbervariations,CNVs)与肺动脉高压(pulmonary hypertension,PAH)的关系,为PAH的发病机制提供科学理论依据。方法以来自中国南方587例PAH患者作为病例组和736例健康对照者作为对照组,TaqMan方法检测ANRIL CNVs的基因型,分析其与PAH发病的相性;通过系列生物学实验揭示阳性CNV影响PAH发生的分子机制。结果 ANRIL CNV-2738282与人群PAH发病存在显著关联,其拷贝数缺失能降低PAH的发病风险(OR=0.40,95%CI:0.31～0.53)。CNV-2738282的拷贝数缺失可降低ANRIL表达,进而改变ANRIL对靶基因CARD8的转录调控而影响PAH发生。结论 ANRIL CNV-2738282与PAH发病有关,可作为人群PAH易感评估的生物标志物。更多还原

【Abstract】 Objective To investigate the relationship between 9p21.3 non-coding RNA(LncRNA ANRIL)copy number variations(CNVs)and pulmonary hypertension(PAH),and provide a scientific theoretical basis for the pathogenesis of PAH.Methods Based on a case-control study of 587 PAH patients as the case group and 736healthy adults as the control group in southern China,the genotype of ANRIL CNVs was detected by TaqMan method,and the correlation between ANRIL CNVs and PAH was analyzed.A series of biological experiments revealed that CNVs were the molecular mechanism affecting the occurrence of PAH.Results ANRIL CNV-2738282 was significantly associated with the incidence of PAH in the population.Loss of copy number could reduce the risk of PAH(OR=0.40,95%CI:0.31～0.53).The deletion of CNV-2738282 copy number can decrease the expression of ANRIL,and then alter the transcriptional regulation of target gene CARD8 by ANRIL,thus affect the occurrence of PAH.Conclusion ANRIL CNV-2738282 is associated with PAH and can be used as a biomarker for PAH susceptibility assessment.更多还原