ACE基因插入/缺失多态与国人肺血栓栓塞症的关联研究

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(ID)多态是否与肺血栓栓塞症存在关联，D等位基因是否增加国人肺血栓栓塞的危险。方法放射性核素肺通气-灌注扫描和(或)超高速CT检查并结合临床资料确诊的肺血栓栓塞症患者72例及性别、年龄匹配的健康对照者72名。调查静脉血栓形成和肺栓塞相关危险因素。酚-氯仿法提取基因组DNA，聚合酶链反应(PCR)鉴定ACE基因I/D多态点基因型。结果(1)病例组外伤、手术史及下肢静脉炎、静脉曲张发生率显著高于对照组，肺血栓栓塞家族史、心血管疾病家族史、口服避孕药、吸烟及饮酒史两组间差异无显著性。(2)健康对照组I、D等位基因频率分别为66％和34％，基因型分布符合Hardy-Weinberg平衡。Ⅱ、ID和DD基因型及I、D等位基因频率在病例和对照组差异无显著性。(3)进一步分别按显性、隐性和加性作用方式探讨ACE基因I/D多态与肺血栓栓塞症的关系，发现DD基因型个体肺栓塞危险显著增加(OR=2.51，P＜0.05)，提示D等位基因为隐性作用方式。(4)将肺血栓栓塞患者按有无明确静脉血栓形成及肺栓塞环境诱因分组，结果显示无明确环境诱因组DD基因型频率显著高于对照组(27.1％vs14.3％；OR=2.64，P＜0.05)，而有明确环境诱因组与对照组相比DD基因型频率差异无显著性。将肺血栓栓塞患者按是否合并下肢静脉血栓形成分组，结果显示肺栓塞合并下肢静脉血栓形成组DD基因型频率显著高于健康对照组(32.4％vs14.3％；OR=3.36，P＜0.05)，单纯肺栓塞组与健康对照组比较差异无显著性。结论ACE基因I/D多态与国人肺血栓栓塞有关，D等位基因为隐性作用方式。DD基因型显著增加无明确静脉血栓形成及肺栓塞环境诱因个体肺栓塞危险；有下肢静脉血栓形成病史的DD基因型个体肺栓塞危险亦显著增加。

Insertion/deletion polymorphsim of the angiotensin I converting enzyme gene and pulmonary thromboembolism in Chinese population

Objective To investigate whether there is an association between the insertiondeletion polymorphsim of human angiotensin I converting enzyme gene(ACE) and pulmonary thromboembolism and whether D allele increases the risk of pulmonary thromboembolism in Chinese population. Methods Seventy two patients with pulmonary thromboembolism and 72 sex and age matched healthy controls were recruited in this study, all patients were diagnosed by lung ventilation/perfusion scan and/or ultrafast CT as well as medical history Risk factors of venous thrombosis and pulmonary thromboembolism were inquired Genome DNA was extracted from whole blood using phenol chloroform Subjects were genotyped for the I/D polymorphism of ACE gene using polymerase chain reaction based restriction fragment length polymorphism analysis. Results (1) The incidences of trauma, operation, phlebitis and venous varicose were significant higher in the patient than in controls No significant difference were found in the family history of pulmonary thromboembolism and cardiovascular diseases, personal history of oral contraceptive, cigarette smoking and alcohol drinking between the patient and controls (2) Frequencies of allele I and D in the controls were 0 66 and 0 34 respectively, the distribution of genotypes met the in Hardy Weinberg equilibrium No significant differences were found in the frequencies of genotype II, ID and DD between patients and controls (3) The recessive allele model was informative and the odds ratio of DD genotype was 2 51( P <0 05) compared with the other two genotypes (4) After further stratification, we found DD genotype was bound to be associated with an 2 64 fold risk of pulmonary thromboembolism for those individuals without existing traditional environmental risk factors and 3 36 fold risk for individuals with medical history of venous thrombosis( P <0 05) Conclusion This study shows that I/D polymorphism of ACE gene is associated with pulmonary thromboembolism in Chinese population and allele D is recessive Our results indicate that DD genotype increases the risk of pulmonary thromboembolism for individuals who have no traditional risk factors of venous thrombosis or pulmonary thromboembolism and also for those with personal history of venous thrombosis