中国肥厚性心肌病的修饰基因.pptVIP

Hypertrophic Cardiomyopathy in China-modifier gene Hui Rutai MD Beijing FuWai Hospital Chinese Academy of Medical Sciences Am J Med 2004,116：63-65 1 million patients, 4 millions geneticlly affected Gene diagnosis prognosis 1.Preclinical diagnosis 2.Selective birth control 3. Predictive prognosis 携带MYH7和MYBPC3基因突变患者的6年随访结果王曙霞，惠汝太等. Clin Cardiol. 2008; 31(3):114 MYH7头部、杆部及MYBPC3基因突变患者的Kaplan-Meier生存曲线王曙霞，惠汝太等，Clin Cardiol. 2008;31:114 高血压是LVH的最主要原因，血压占左心室重量变异的25％ 遗传因素占独立于血压之外的左心室重量变异的60％  线粒体氧化长链脂肪酸产生ATP是成人心肌能量的主要来源。成体心脏大约60－90％的ATP来源于脂肪酸氧化（FAO)。 在不同的发育时期和生理/病理生理状态下，心脏的能量代谢选择有所不同。 能量调节的转变主要是通过参与脂肪酸利用的基因表达来实现的。而 peroxisome proliferator-activated receptors(PPARs)，及PGC1α(proliferators-activated receptor-γ coactivator-1α (PGC-1α) gene )是心脏脂肪酸代谢的关键的调节因子 。 PGC1-? Gly482Ser (rs8192678) HCM、LVH as well as HT PGC1-? Thr394Thr（rs2970847）and HCM 、LVHas well as HT PPAR-α基因的rs9615784、rs4253654 rs4253778多态位点；以及PPAR-γ基因的Pro12Ala 、rs7649970和rs4135245多态位点均与HCM、LVH和HT无关联，用logistic回归模型校正了传统的危险因素后，仍无相关性。 结 论 PGC-1α基因Gly482Ser变异和Thr394Thr多态与HCM发病风险增加相关联； PPAR-α和PPAR-γ基因及PGC-1α基因的多态性均不增加LVH发生的风险； PGC-1α基因可能为HCM的修饰基因。 Not associated with hypertension A total of 261 consecutive HCM patients and 609 healthy controls were enrolled into this study. We have genotyped 7 SNPs of ACE2, of which 2 SNPs (rs4646156, rs233575) were proved to be not polymorphic in Chinese population. The minor alleles of other 3 SNPs (rs4646140, rs879922 and rs4240157) were too low (0.01) in Chinese population. At last, 2 SNPs (rs2106809 and rs6632677) were successfully genotyped. ACE2 polymorphism The odd ratios of rs2106809 and rs6632677 for HCM haplotype in men SNP genotype OR*(95% CI) P value Rs2106809 T 1.34(1.01?1.77) 0.04 Rs6632677 C 1.11(1.03?1.21) 0.002 Haplotype TC 1.59(1.21?1.87) 0.001 *Adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure. The polymorphisms of ACE2