当科助教多田隼人先生らが執筆しました冠動脈疾患、脂質異常症と新しい遺伝子異常背景に関します総説論文が出版されました。

Tada H, Kawashiri MA, Konno T, Yamagishi M, Hayashi K.
Common and Rare Variant Association Study for Plasma Lipids and Coronary Artery Disease.
J Atheroscler Thromb. 2016;23(3):241-56. 
Abstract
Blood lipid levels are highly heritable and modifiable risk factors for coronary artery disease (CAD), and are the leading cause of death worldwide. These facts have motivated human genetic association studies that have the substantial potential to define the risk factors that are causal and to identify pathways and therapeutic targets for lipids and CAD.The success of the HapMap project that provided an extensive catalog of human genetic variations and the development of microarray based genotyping chips (typically containing variations with allele frequencies ＞5%) facilitated common variant association study (CVAS; formerly termed genome-wide association study, GWAS) identifying disease-associated variants in a genome-wide manner. To date, 157 loci associated with blood lipids and 46 loci with CAD have been successfully identified, accounting for approximately 12%-14% of heritability for lipids and 10% of heritability for CAD. However, there is yet a major challenge termed “missing heritability problem,” namely the observation that loci detected by CVAS explain only a small fraction of the inferred genetic variations. To explain such missing portions, focuses in genetic association studies have shifted from common to rare variants. However, it is challenging to apply rare variant association study (RVAS) in an unbiased manner because such variants typically lack the sufficient number to be identified statistically.In this review, we provide a current understanding of the genetic architecture mostly derived from CVAS, and several updates on the progress and limitations of RVAS for lipids and CAD

従来、家族性高コレステロール血症、肥大型心筋症、遺伝性不整脈症候群などを代表とします、メンディリアン型の遺伝を示す疾患については、限られた領域の遺伝子変異が表現系を規定することから、少数の症例からでも原因遺伝子の特定が可能でした。しかし、広義の冠動脈疾患、糖尿病、高血圧など、多因子が関与する疾患群においては必ずしも原因遺伝子の特定は容易ではありませんでした。最近のGWAS, Whole genome解析など、従来の手法では困難であった疾患群での原因、あるいは疾患発症関連遺伝子の検索がひろくなされるようになってきました。当教室の多田、川尻、今野、林氏らはこれまで、メンディリアン型遺伝性疾患の原因遺伝子の特定や機能解析に従事してきました。かかる、実績をもとに、最近の遺伝子診断から疾患の0次予防への展望を解説しています。是非ご一読いただければと推薦いたします。

関連文献
Hayashi K, Konno T, Tada H, et al. Functional Characterization of Rare Variants Implicated in Susceptibility to Lone Atrial Fibrillation.
Circ Arrhythm Electrophysiol. 2015 Oct;8(5):1095-104. 

Konno T, Hayashi K, Fujino N, et al. Electrocardiographic QRS Fragmentation as a Marker for Myocardial Fibrosis in Hypertrophic Cardiomyopathy.
J Cardiovasc Electrophysiol. 2015 Jun 22.  

Kawashiri MA, Tada H, Hashimoto M, et al. Extreme Contrast of Postprandial Remnant-Like Particles Formed in Abetalipoproteinemia and Homozygous Familial Hypobetalipoproteinemia.
JIMD Rep. 2015;22:85-94.