循環器ジャーナル68巻1号

2020年01月発行

特集 U40世代が描く心不全診療の現状と未来—基礎研究を識り，臨床を素心深考する Ⅳ．基礎研究から知る臨床の未来

ゲノム研究はどこまで進んでいるの？

著者： 野村征太郎¹

所属機関： ¹東京大学医学部附属病院循環器内科

ページ範囲：P.170 - P.175

Point
・循環器疾患は遺伝要因と環境要因の組み合わせにより発症する．
・LMNA遺伝子変異は拡張型心筋症の予後を規定しており，精密医療として実用化されることが期待される．
・一塩基多型（SNPs）のポリジェニック・リスクスコアにより虚血性心疾患・心房細動のリスク層別化が期待される．

参考文献

1) Geisterfer-Lowrance AA, Kass S, Tanigawa G, et al:A molecular basis for familial hypertrophic cardiomyopathy:a beta cardiac myosin heavy chain gene missense mutation. Cell 62:999-1006, 1990

2) Hershberger RE, Givertz MM, Ho CY, et al:Genetic evaluation of cardiomyopathy:a clinical practice resource of the American College of Medical Genetics and Genomics（ACMG）. Genet Med 20:899-909, 2018

3) Yotti R, Seidman CE, Seidman JG:Advances in the Genetic Basis and Pathogenesis of Sarcomere Cardiomyopathies. Annu Rev Genomics Hum Genet 20:129-153, 2019

4) Tobita T, Nomura S, Fujita T, et al:Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling. Sci Rep 8:1998, 2018

5) 日本循環器学会：心筋症診療ガイドライン（2018年改訂版）．　http://www.j-circ.or.jp/guideline/pdf/JCS2018_tsutsui_kitaoka.pdf

6) Priori SG, Blomström-Lundqvist C, Mazzanti A, et al:2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J 36:2793-2867, 2015

7) Tobita T, Nomura S, Morita H, et al:Identification of MYLK3 mutations in familial dilated cardiomyopathy. Sci Rep 7:17495, 2017

8) Ware JS, Amor-Salamanca A, Tayal U, et al:Genetic Etiology for Alcohol-Induced Cardiac Toxicity. J Am Coll Cardiol 71:2293-2302, 2018

9) Ware JS, Li J, Mazaika E, et al:Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies. N Engl J Med 374:233-241, 2016

10) Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, et al:Genetic Variants Associated With Cancer Therapy-Induced Cardiomyopathy. Circulation 140:31-41, 2019

11) Herman DS, Lam L, Taylor MR, et al:Truncations of titin causing dilated cardiomyopathy. N Engl J Med 366:619-628, 2012

12) Schafer S, de Marvao A, Adami E, et al:Titin-truncating variants affect heart function in disease cohorts and the general population. Nat Genet 49:46-53, 2017

13) Haggerty CM, Damrauer SM, Levin MG, et al:Genomics-First Evaluation of Heart Disease Associated With Titin-Truncating Variants. Circulation1 40:42-54, 2019

14) Choi SH, Weng LC, Roselli C, et al:Association Between Titin Loss-of-Function Variants and Early-Onset Atrial Fibrillation. JAMA 320:2354-2364, 2018

15) Low SK, Takahashi A, Ebana Y, et al:Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nat Genet 49:953-958, 2017

16) Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al:Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet 50:1234-1239, 2018

17) Samani NJ, Erdmann J, Hall AS, et al:Genomewide association analysis of coronary artery disease. N Engl J Med 357:443-453, 2007

18) van Arensbergen J, Pagie L, FitzPatrick VD, et al:High-throughput identification of human SNPs affecting regulatory element activity. Nat Genet 51:1160-1169, 2019

19) Khera AV, Kathiresan S:Genetics of coronary artery disease:discovery, biology and clinical translation. Nat Rev Genet 18:331-344, 2017

20) Khera AV, Chaffin M, Aragam KG, et al:Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 50:1219-1224, 2018

21) Martin AR, Gignoux CR, Walters RK, et al:Human Demographic History Impacts Genetic Risk Prediction across Diverse Populations. Am J Hum Genet 100:635-649, 2017

22) Do R, Stitziel NO, Won HH, et al:Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction. Nature 518:102-106, 2015

23) Tajima T, Morita H, Ito K, et al:Blood lipid-related low-frequency variants in LDLR and PCSK9 are associated with onset age and risk of myocardial infarction in Japanese. Sci Rep 8:8107, 2018

24) Musunuru K, Kathiresan S:Genetics of Common, Complex Coronary Artery Disease. Cell. 177:132-145, 2019

25) Ko T, Fujita K, Nomura S, et al:Quantification of DNA Damage in Heart Tissue as a Novel Prediction Tool for Therapeutic Prognosis of Patients with Dilated Cardiomyopathy. JACC Basic Transl Sci. in press.