複数の新型トロンボスポンディン遺伝子の単一の核酸多形態は,家族性早発性心筋梗塞と関連している可能性があります

E J Topol¹, J McCarthy, S Gabriel

¹Cleveland Clinic Foundation, Cleveland, Ohio, USA. topole@ccf.org

Circulation

|November 28, 2001

まとめ

トロンボスポンディン遺伝子ファミリーの遺伝的変異は,早発性冠動脈疾患と関連しています. トロンボスポンディン遺伝子の新型変異は,家族性心筋梗塞との関連を示しており,さらなる研究が必要である.

科学分野:

遺伝学遺伝学とは
心血管疾患に関する研究
分子生物学は分子生物学である.

背景:

高通量ゲノミクスは,早発性冠動脈疾患 (CAD) などの疾患における遺伝的変異をカタログ化することを可能にします.
遺伝的傾向を理解することは,早期発症の心臓病のリスクのある個人を特定するために重要です.

研究の目的:

血管生物学遺伝子の新しい遺伝子変異と早発性冠動脈疾患 (CAD) の関連性を調査する.
家族性心筋梗塞 (FMI) と潜在的に関連している特定のトロンボスポンディン遺伝子変異を特定する.

主な方法:

早期CADの398の家族における62の血管生物学遺伝子の62の単核酸多形態 (SNPs) のゲノム解析.
心筋梗塞,再血管化,または45歳 (男性) または50歳 (女性) 以前の重要な冠動脈損傷に関連したSNPを特定するための統計的関連検査.

主要な成果:

トロンボスポンジンの3つのファミリーの新規変異は,早発性CADと関連していました.
トロンボスポンジン4 (THBS4) ミッセンスの変種 (A387P) は,MI (OR=1.89,P=0.002) と最も強い関連性を示した.
Thrombospondin 2 (THBS2) 3' UTRの変種は,MIに対する保護効果を示した (OR=0.31,P=0.0018),THBS1のミスセンスの変種 (N700S) は,CADのリスクの増加 (OR=11.90,P=0.041) と関連していた.

結論:

トロンボスポンディン遺伝子ファミリー内の複数の新規変異は,家族性早発性心筋梗塞との潜在的な関連を示しています.
トロンボスポンディンと高通量ゲノム技術により,家族性心不全性疾患の文脈でさらなる調査が求められます.

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