大規模で稀な染色体欠損は,重度の早期発症肥満と関連しています
Elena G Bochukova1, Ni Huang, Julia Keogh
1University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
Nature
|December 8, 2009
まとめ
コピーの数の変動,特に大きな削除は,重度の肥満と有意に関連しています. これらの遺伝的変化,特に染色体16p11.2の変化は,患者の過食症とインスリン抵抗性に関連しています.
科学分野:
- 遺伝学 遺伝学とは
- 人間の生理学 人間生理学
- 医学研究 医学研究
背景:
- 肥満は複雑で,遺伝性の高い疾患であり,有意な遺伝的異質性を持っています.
- 早期発症の重度の肥満の遺伝的基盤を理解することは,標的を絞った介入の開発に不可欠です.
研究 の 目的:
- 重度の早期発症肥満の遺伝的基礎に対するコピー数変異 (CNVs) の寄与を調査する.
- 重度の肥満,特に発達遅延の患者に関連する特定のまれなCNVを特定する.
主な方法:
- 重度の早期発症肥満の300人の白人の患者と7,366人の対照群における大規模 (>500kb) 希少 (<1%) 欠損の比較分析.
- 重度の肥満患者1,062人の独立したコホートにおける再発性CNVの特定と検証.
- SH2B1.1.を含む染色体16p11.2の欠損および関連する遺伝子の遺伝子解析.
主要な成果:
- 希少で大きな欠損は,重度の肥満の患者では,対照群と比較して有意に濃縮された (P <0.001).
- 16p11.2染色体での再発性欠損は,患者で確認され,5つの症例で重複する欠損が確認されました.
- 削除キャリアは,肥満の重度とは関係なく,過食症と重度のインスリン抵抗性を示し,SH2B1のような遺伝子が代謝失調に関与している.
結論:
- コピー番号の多様性は,ヒトの肥満の遺伝的構造に重要な役割を果たしています.
- 16p11.2染色体にあるような特定のCNVは,重度の肥満および関連する代謝現象型と関連しています.
- この発見は,重度の肥満における遺伝的要因の重要性を強調し,潜在的な治療目標を示唆しています.
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