単一遺伝子の変異と,コミュニティにおける左心房壁の厚さの増加:フレミングハム心臓研究
Hiroyuki Morita1, Martin G Larson, Scott C Barr
1The Program in Genomics Applications: CardioGenomics Group--Department of Genetics, NRB Room 256, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Circulation
|June 7, 2006
まとめ
サルコメアと貯蔵遺伝子の遺伝的変異は,説明不可能な左心室壁の厚さ (LVWT) の増加を伴うコミュニティ個人の18%で見つかりました. これは,遺伝的要因がLVWTの異質性に寄与することを示唆しています.
科学分野:
- 心臓病学 心臓病学
- 遺伝学 遺伝学とは
- 分子生物学は分子生物学である.
背景:
- 稀な家族性心筋病は,サルコメアタンパク質,PRKAG2,LAMP2,アルファ-ガラクトシダゼA (GLA),およびミトコンドリア遺伝子の変異から生じる可能性があります.
- 一般社会における左心房壁の厚さ (LVWT) の増加に対するこれらの遺伝的原因の流行は,特徴づけられていないままです.
研究 の 目的:
- コミュニティベースのコホートで,既知の心筋病変に関連した遺伝子が,説明不可能な増加したLVWTに与える寄与を調査する.
- 増加したLVWTを有する個体におけるサルコメアタンパク質と貯蔵遺伝子変異の頻度を決定する.
主な方法:
- 1862年のフレミングハム心臓研究 (Framingham Heart Study) の参加者の中で,サルコメアタンパク質の8つの遺伝子,3つの貯蔵心筋病を引き起こす遺伝子,そして27のミトコンドリア遺伝子を配列化した.
- 原因不明のLVWT増加 (最大LVWT>13mm),重度の高血圧または有意な大動脈疾患のない被験者を特定しました.
- 50人の適格な参加者の遺伝子変異を分析し,原因不明のLVWT増加を示した.
主要な成果:
- 9人の個体 (2人の女性) で8つの変異が特定され,原因不明のLVWTが増加しました.
- サルコメアタンパク質の5つの遺伝子 (MYH7,MYBPC3,TNNT2,TNNI3,MYL3) で7つの変異が見つかりました.
- 1つのアルファ-ガラクトシダゼA (GLA) 変異が検出されました. 変異を有する個体は,変異のない個体と臨床的に類似していました.
結論:
- コミュニティコホートの約3%がLVWTを増加させ,これらの症例の18%がサルコメアタンパク質または脂質貯蔵遺伝子変異に関連していた.
- コミュニティ内のLVWTの増加は異質な状態です.
- 様々な遺伝子の単一遺伝子変異は,増加したLVWTの原因である可能性があります.
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