汉族人群中与特发性肺动脉高压相关的KCNA5基因变异  

Genetic variants of KCNA5 in patients of Chinese Han nationality with idiopathic pulmonary arterial hypertension

作　　者：张颖[1] 何建国[1] 浦介麟[1] 张建强[1] 柳志红[1] 熊长明 倪新海[1] 

机构地区：[1]北京协和医学院,中国医学科学院,阜外心血管病医院病理与生理实验中心,北京市100037

出　　处：《中华老年多器官疾病杂志》2009年第4期333-337,共5页Chinese Journal of Multiple Organ Diseases in the Elderly

基　　金：国家973重点基础研究项目(2007CB512008);国家"十一五"科技支撑项目(2006BAI01A07)

摘　　要：目的探讨中国汉族人群中与特发性肺动脉高压(IPAH)发病和进展有关的KCNA5基因变异。方法将86例特发性肺动脉高压患者作为病例组,250例正常人作为对照组。所有参与者抽取5ml外周静脉血,提取基因组DNA。通过对KCNA5基因序列测序寻找在病例组和对照组中基因位点频率具有显著性差异的基因变异。所有患者进行右心导管检查记录肺血流动力学数据,然后按照有无基因变异将患者分成两组,比较两组患者肺血流动力学指标。结果位于编码区的KCNA5 C-862G频率在患者和对照组之间有显著性差异。具有该位点变异的患者平均肺动脉压、肺血管阻力显著升高。结论KCNA5基因编码区单核苷酸多态位点g.862C>G可能会影响Kv1.5通道的表达和功能,从而与特发性肺动脉高压发病和进展相关联。Objective To investigate the relevance of genetic alterations in the Kvl. 5 channel gene （KCNA5） to the development of idiopathic pulmonary arterial hypertension（IPAH） in Chinese Han nationality. Methods IPAH patients （n=86） were recruited from Chinese Han nationality. Randomized control samples （n=250） were ob- tained from the same population. Genomic DNA was extracted from peripheral blood of all samples. The coding, the noncoding regions and the enhancer region of the KCNA5 gene were amplified by using primers sets with optimal annealing temperature. All amplificants were directly sequenced. Hemodynamic data were compared between patients with and without KCNA5 gene variants. Results The frequency of the variant KCNA5 C-862G was found statisti- cally different between the patients and the control samples. Moreover, there was marked difference between the patients with and without the variant. Conclusion Genetic variant KCNA5 C-862G may alter the expression and/or function of Kvl. 5 channel, which may be associated with IPAH of phenotype.

关 键 词：高血压 肺性 KCNA5基因 肌细胞 平滑肌 

分 类 号：R581[医药卫生—内分泌] R394[医药卫生—内科学]