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1、Hypertrophic Cardiomyopathy in China-modifier gene,Hui Rutai MD Beijing FuWai Hospital Chinese Academy of Medical Sciences,负担,Big burden,Am J Med 2004,116：63-65,1 million patients, 4 millions geneticlly affected,Gene mutations were identified in 27 pedigrees among 51 FHCM (53%) and 12 in 49 sporadic
2、 HCM (25%).,Mutation prevalence in Chinese and Caucasian,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,*The major intervention included surgical septal myectomy, Alcohol septal a
3、blation and DDD pacemaker,携带MYH7和MYBPC3基因突变而无临床症状者 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,Modifier Genes,相同突变：临床表现、治疗反应的异质性：基因突变类型，修饰基因，环境因素； 干预靶点：改变修饰基因表达,1)王曙霞惠汝太等: PPAR- Coactivator-1alpha : Clin Chem 329(2):796-9
4、.,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6090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PGC1(proliferators-activated receptor- coactivator-1 (PGC-1) gene )是心脏脂
5、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-基因的rs9615784、rs4253654 rs4253778多态位点；以及PPAR-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-1基因Gly482Ser变异和Thr394Thr多态与HCM发病风险增加相关联；
6、PPAR-和PPAR-基因及PGC-1基因的多态性均不增加LVH发生的风险； PGC-1基因可能为HCM的修饰基因。 Not associated with hypertension,ACE2 in RAS,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 polymo
7、rphic 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 SN
8、P genotype OR*(95% CI) P value Rs2106809 T 1.34(1.011.77) 0.04 Rs6632677 C 1.11(1.031.21) 0.002 Haplotype TC 1.59(1.211.87) 0.001 *Adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure.,The polymorphisms of ACE2 are associated with the magnitude of hypertrophy of HCM in men,ACE2 gene is mapped to the X chromosome which may have different effects on men and women.,科技部中德分子医学研究室暨教育部基因与临床重点室 科技部/国家外专局国家级国际合作研究中心,