medicina61巻8号

2024年07月発行

特集 “とりあえずスタチン”から脱却！—動脈硬化性疾患一次予防・最新の考え方 診断

遺伝子診断の展望—脂質異常単一遺伝子疾患から多因子疾患

著者： 多田隼人¹

所属機関： ¹金沢大学附属病院循環器内科

ページ範囲：P.1234 - P.1239

Point
◎脂質異常症や冠動脈疾患は遺伝しうる形質であり，遺伝子診断はきわめて有用である．
◎遺伝子診断により，リスク層別化につながる場合がある．
◎高頻度遺伝子多型（SNV）に基づくpolygenic risk scoreと呼ばれる考え方が登場した．

参考文献

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2）多田隼人：遺伝学から動脈硬化性疾患を考える．日内科誌 112：194-201, 2023

3）Mabuchi H, et al：Molecular genetic epidemiology of homozygous familial hypercholesterolemia in the Hokuriku district of Japan. Atherosclerosis 214：404-407, 2011 PMID 21146822

4）Tada H, et al：Impact of clinical signs and genetic diagnosis of familial hypercholesterolaemia on the prevalence of coronary artery disease in patients with severe hypercholesterolaemia. Eur Heart J 38：1573-1579, 2017 PMID 28159968

5）Tada H, et al：Oligogenic familial hypercholesterolemia, LDL cholesterol, and coronary artery disease. J Clin Lipidol 12：1436-1444, 2018 PMID 30241732

6）Nomura A, et al：Impact of genetic testing on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia（GenTLe-FH）；A randomised waiting list controlled open-label study protocol. BMJ Open 8：e023636, 2018 PMID 30593551

7）Tada H, et al：Genetic counseling and genetic testing for familial hypercholesterolemia. Genes（Basel） 15：297, 2024 PMID 38540356

8）Nomura A, et al：Impact of providing genetics-based future cardiovascular risk on LDL-C in patients with familial hypercholesterolemia. J Clin Lipidol 17：622-632, 2023 PMID 37673778

9）Tada H, et al：Risk prediction by genetic risk scores for coronary heart disease is independent of self-reported family history. Eur Heart J 37：561-567, 2016 PMID 26392438

10）Khera AV, et al：Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 50：1219-1224, 2018 PMID 30104762

11）Khera AV, et al：Whole-genome sequencing to characterize monogenic and polygenic contributions in patients hospitalized with early-onset myocardial infarction. Circulation 139：1593-1602, 2019 PMID 30586733

12）Mega JL, et al：Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy；An analysis of primary and secondary prevention trials. Lancet 385：2264-2271, 2015 PMID 25748612

13）Khera AV, et al：Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med 375：2349-2358, 2016 PMID 27959714