中国肥厚性心肌病的修饰基因课件

1、Hypertrophic Cardiomyopathy in China-modifier gene Hui Rutai MD Beijing FuWai Hospital Chinese Academy of Medical Sciences负担Big burdenAm J Med 2004,116：63-651 million patients,4 millions geneticlly affected Gene mutations were identified in 27 pedigrees among 51 FHCM (53%) and 12 in 49 sporadic HCM

2、(25%).Genes FrequencyCaucasian*Chinese Mutation prevalence in Chinese and Caucasian -MHC3050%24%cMyBPC1520%11%cTnT1520%1%cTnI5%3%-Tm5%EMLC5%RMLC5%Cardiac -actin5%K-voltage-gated channelRareTitin5%PKA-?-MHCRaremtDNARareGene diagnosis & prognosis1.Preclinical diagnosis2.Selective birth control3. Predi

3、ctive prognosisMYH7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;31:114Modifier 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 & Lab Med. 2007, 45:962. 2)王曙霞惠汝太等: ACE2: Chin Med J2008;121(1):27 3) 王萍，惠汝太等：MYBPC3. BBRC. 2005,8;32

4、9(2):796-9. 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60PGC1- Thr394Thr（rs2970847）and HCM 、LVHas well as HT人群基因型, n (%)CC 基因型TTCTCC频率Crude OR(95% CI)Adjusted OR(95% CI)对照组, n=89468(7.6)382(42.7)444(49.7)49.711HCM, n=27015(5.6)95(35.2)160(59.3)59.31.46(1.10-1.94)*1.49(1.15-1.98)*LVH, n=118080(

5、6.8)418(35.4)682(57.8)57.81.39(1.17-1.65)*1.21(0.84-1.76)HT, n=130689(6.8)514(39.4)703(53.8)53.81.18(1.00-1.40)1.31(0.81-2.12)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

6、加相关联；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 hypertensionACE2 in RASACE2 polymorphismThe odd ratios of rs2106809 and rs6632677 for HCM haplotype in menSNP genotype OR*(95% CI) P valueRs2106809 T 1.34(1.011.77) 0.04Rs6632677 C 1.11(1.031.21) 0.002Haplotype TC 1.59

7、(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 populationrs2106809menwomenCTp valuesCCCTTTp valuesMaximal wall thickness(mm)17.95.520.06.30.0319.86.018.25.019.96.10.64PW(mm)10.42.611.13.80.1910.54.110.92.810.82.70.89LVIDD(mm)46.37.044.06.60.0641.86.845.38.241.95.10.19SBP123.217.0123.1210.97112.321118.726114.7220.57DBP79.311.677.411.80.3873.51573.715.374.111.10.99 ACE2 gene is