線維細胞成長因子1遺伝子と高血圧:定量的な特徴の場所から位置分析まで
Maciej Tomaszewski1, Fadi J Charchar, Mark D Lynch
1British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK. mt142@le.ac.uk
Circulation
|October 3, 2007
まとめ
線維細胞成長因子1遺伝子 (FGF1) の遺伝的変異は高血圧に関連しています. 高血圧患者における腎臓FGF1発現の増加は,血圧調節における役割を示唆しています.
科学分野:
- 遺伝学 遺伝学とは
- 心血管疾患 心血管疾患
- 分子生物学は分子生物学である.
背景:
- 染色体5の長い腕は高血圧と関連しており,血圧を調節する遺伝子を宿している.
- 以前の研究では,この染色体領域が高血圧と関連していた.
研究 の 目的:
- 高血圧に関連する特定の遺伝子と遺伝的変異を特定する.
- 血圧調節におけるフィブロブラスト成長因子1 (FGF1) の役割を調査する.
主な方法:
- マイクロサテライトマーカーの精細なマッピングと,単一ヌクレオチドポリモルフィズム (SNP) を使用したリンク不均衡マッピング.
- ファミリーベースの関連分析と定量ポリメラーゼ連鎖反応 (qPCR) と遺伝子発現分析のためのウエスタン・ブロッティング.
- FGF1の局所を決定するための腎臓免疫ヒストケミストリー.
主要な成果:
- 結合分析は,染色体5の領域と血圧 (Z=3.51,P=0.0002) の関連性を確認した.
- フィブロブラスト成長因子1 (FGF1) はポジショナルの候補遺伝子として特定されました.
- FGF1の遺伝的変異,特にイントロニックSNP rs152524は,高血圧 (P=0.0026) と有意に関連していました.
- 高血圧患者は,正常血圧対照群と比較して,腎臓FGF1 mRNAおよびタンパク質発現の増加を示した.
- FGF1の発現は,腎臓のグルメルーラ内皮細胞とメサンジアル細胞に局限していた.
結論:
- FGF1内の遺伝的変異は,家族の血圧上昇と関連しています.
- 腎臓FGF1発現の上昇は,FGF1と高血圧との関連を媒介する可能性があります.
- これらの発見を検証するために,多様なコホートでのさらなる複製が必要である.
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