-
摘要: 心源性猝死(SCD)可发生于儿童、青少年和成年人。成人SCD常与冠心病相关,而遗传性心脏病则能引起儿童、青少年SCD事件高发。基因突变与遗传性心脏病关系密切且其有助于预测SCD发生风险,遗传性心脏病可能还与单核苷酸多态性有关。了解遗传性心脏病的危险因素并对SCD高危患者进行基因检测,将有助于疾病诊断、更准确的危险分层以及治疗。本文就SCD的遗传学基础作一综述。Abstract: Sudden cardiac death(SCD)may occur in children,adolescents and adults.Adults suffer from SCD often associate with coronary heart disease,however,inherited heart diseases can cause high incidence of SCD in children and adolescents.Inherited heart diseases are closely related with mutations as well as single nucleotide polymorphism,which may help predict the risk of SCD.Understanding the risk factors of inherited heart diseases and performing agenetic testing in high-risk SCD patients will help the diagnosis of a disease,bring more accurate risk stratification and treatments.This article is to review the genetic basis of SCD.
-
Key words:
- sudden cardiac death /
- inherited heart diseases /
- gene
-
[1] KAPPLINGER J D,TESTER D J,ALDERS M,et al.An international compendium of mutations in the SCN5A-encoded cardiac sodium channel in patients referred for Brugada syndrome genetic testing[J].Heart Rhythm,2010,7:33-46.
[2] BEZZINA C R,LAHROUCHI N,PRIORI S G.Genetics of sudden cardiac death[J].Circ Res,2015,116:1919-1936.
[3] PFEUFER A,SANNA S,ARKING D E,et al.Common variants at ten loci modulate the QT interval duration in the QTSCD Study[J].Nat Genet,2009,41:407-414.
[4] ARKING D E,PFEUFER A,POST W,et al.Acommon genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization[J].Nat Genet,2006,38:644-651.
[5] CROTTI L,MONTI M C,INSOLIA R,et al.NOS1AP is a genetic modifier of the long-QT syndrome[J].Circulation,2009,120:1657-1663.
[6] TOMAS M,NAPOLITANO C,DE GIULI L,et al.Polymorphisms in the NOS1AP gene modulate QT interval duration and risk of arrhythmias in the long QTsyndrome[J].J Am Coll Cardiol,2010,55:2745-2752.
[7] DUCHATELET S,CROTTI L,PEAT R A,et al.Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QTsyndrome[J].Circ Cardiovasc Genet,2013,6:354-361.
[8] AMIN A S,GIUDICESSI J R,TIJSEN A J,et al.Variants in the 3'untranslated region of the KCNQ1-encoded Kv7.1potassium channel modify disease severity in patients with type 1long QT syndrome in an allele-specific manner[J].Eur Heart J,2012,33:714-723.
[9] BEZZINA C R,BARC J,MIZUSAWA Y,et al.Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome,a rare disease with high risk of sudden cardiac death[J].Nat Genet,2013,45:1044-1049.
[10] HU D,BARAJAS-MARTINEZ H,PFEIFFER R,et al.Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome[J].J Am Coll Cardiol,2014,64:66-79.
[11] VAN DEN BOOGAARD M,SMEMO S,BURNIC-KA-TUREK O,et al.A common genetic variant within SCN10A modulates cardiac SCN5A expression[J].J Clin Invest,2014,124:1844-1852.
[12] VAN DER WERF C,NEDEREND I,HOFMAN N,et al.Familial evaluation in catecholaminergic polymorphic ventricular tachycardia:disease penetrance and expression in cardiac ryanodine receptor mutationcarrying relatives[J].Circ Arrhythm Electrophysiol,2012,5:748-756.
[13] NYEGAARD M,OVERGAARD M T,SONDER-GAARD M T,et al.Mutations in calmodulin cause ventricular tachycardia and sudden cardiac death[J].Am J Hum Genet,2012,91:703-712.
[14] ROUX-BUISSON N,CACHEUX M,FOUREST-LIEUVIN A,et al.Absence of triadin,aprotein of the calcium release complex,is responsible for cardiac arrhythmia with sudden death in human[J].Hum Mol Genet,2012,21:2759-2767.
[15] MOHLER P J,SPLAWSKI I,NAPOLITANO C,et al.A cardiac arrhythmia syndrome caused by loss of ankyrin-B function[J].Proc Natl Acad Sci U S A,2004,101:9137-9142.
[16] TESTER D J,ARYA P,WILL M,et al.Genotypic heterogeneity and phenotypic mimicry among unrelated patients referred for catecholaminergic polymorphic ventricular tachycardia genetic testing[J].Heart Rhythm,2006,3:800-805.
[17] LOPES L R,RAHMAN M S,ELLIOTT P M.Asystematic review and meta-analysis of genotype-phenotype associations in patients with hypertrophic cardiomyopathy caused by sarcomeric protein mutations[J].Heart,2013,99:1800-1811.
[18] VAN DRIEST S L,VASILE V C,OMMEN S R,et al.Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy[J].JAm Coll Cardiol,2004,44:1903-1910.
[19] JIANG J,WAKIMOTO H,SEIDMAN J G,et al.Allele-specific silencing of mutant Myh6 transcripts in mice suppresses hypertrophic cardiomyopathy[J].Science,2013,342:111-114.
[20] ADSIT G S,VAIDYANATHAN R,GALLER C M,et al.Channelopathies from mutations in the cardiac sodium channel protein complex[J].J Mol Cell Cardiol,2013,61:34-43.
[21] NOORMAN M,HAKIM S,KESSLER E,et al.Remodeling of the cardiac sodium channel,connexin43,and plakoglobin at the intercalated disk in patients with arrhythmogenic cardiomyopathy[J].Heart Rhythm,2013,10:412-419.
[22] SATO P Y,MUSA H,COOMBS W,et al.Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes[J].Circ Res,2009,105:523-526.
[23] FRIEDLANDER Y,SISCOVICK D S,ARBOGASTP,et al.Sudden death and myocardial infarction in first degree relatives as predictors of primary cardiac arrest[J].Atherosclerosis,2002,162:211-216.
[24] DEKKER L R,BEZZINA C R,HENRIQUES J P,et al.Familial sudden death is an important risk factor for primary ventricular fibrillation:a case-control study in acute myocardial infarction patients[J].Circulation,2006,114:1140-1145.
[25] KAIKKONEN K S,KORTELAINEN M L,LINNAE,et al.Family history and the risk of sudden cardiac death as a manifestation of an acute coronary event[J].Circulation,2006,114:1462-1467.
[26] XIONG Q,CAO L,HU J,et al.A rare loss-of-function SCN5A variant is associated with lidocaine-induced ventricular fibrillation[J].Pharmacogenomics J,2014,14:372-375.
[27] BEZZINA C R,PAZOKI R,BARDAI A,et al.Genome-wide association study identifies a susceptibility locus at 21q21 for ventricular fibrillation in acute myocardial infarction[J].Nat Genet,2010,42:688-691.
[28] ARKING D E,JUNTTILA M J,GOYETTE P,et al.Identification of a sudden cardiac death susceptibility locus at 2q24.2 through genome-wide association in European ancestry individuals[J].PLoS Genet,2011,7:e1002158.
[29] MARSMAN R F,BEZZINA C R,FREIBERG F,et al.Coxsackie and adenovirus receptor is a modifier of cardiac conduction and arrhythmia vulnerability in the setting of myocardial ischemia[J].J Am Coll Cardiol,2014,63:549-559.
[30] BUGERT P,ELMAS E,STACH K,et al.No evidence for an association between the rs2824292 variant at chromosome 21q21 and ventricular fibrillation during acute myocardial infarction in a German population[J].Clin Chem Lab Med,2011,49:1237-1239.
[31] BELL C J,DINWIDDIE D L,MILLER N A,et al.Carrier testing for severe childhood recessive diseases by next-generation sequencing[J].Sci Transl Med,2011,3:64r-65r.
计量
- 文章访问数: 187
- PDF下载数: 18
- 施引文献: 0