中國肥厚性心肌病的修飾基因課件

1、Hypertrophic Cardiomyopathy in China-modifier gene Hui Rutai MD Beijing FuWai Hospital Chinese Academy of Medical Sciences負擔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頭部、桿部及MYBPC3基因突變患者的Kaplan-Meier生存曲線王曙霞，惠汝太等，Clin Cardiol. 2008;31:114Modifier Genes相同突變：臨床表現(xiàn)、治療反應的異質(zhì)性：基因突變類型，修飾基因，環(huán)境因素；干預靶點：改變修飾基因表達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. 高血壓是LVH的最主要原因，血壓占左心室重量變異的25 遺傳因素占獨立于血壓之外的左心室重量變異的60PGC1- Thr394Thr（rs2970847）and HCM 、LVHas well as HT人群基因型, n (%)CC 基因型TTCTCC頻率Crude OR(95% CI)Adjusted OR(95% CI)對照組, 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多態(tài)位點；以及PPAR-基因的Pro12Ala 、rs7649970和rs4135245多態(tài)位點均與HCM、LVH和HT無關聯(lián)，用logistic回歸模型校正了傳統(tǒng)的危險因素后，仍無相關性。結(jié) 論PGC-1基因Gly482Ser變異和Thr394Thr多態(tài)與HCM發(fā)病風險增

6、加相關聯(lián)；PPAR-和PPAR-基因及PGC-1基因的多態(tài)性均不增加LVH發(fā)生的風險；PGC-1基因可能為HCM的修飾基因。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