目的 本项目拟探索位 9p21.3 的非编码 RNA（LncRNA ANRIL）拷贝数变异（copy⁃number variations，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。

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 736 healthy adults as the control group in southern China，the genotype of ANRIL CNVs was detected by TaqMan meth⁃ od，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 occur⁃ rence of PAH. Conclusion ANRIL CNV ⁃2738282 is associated with PAH and can be used as a biomarker for PAH susceptibility assessment.