関連する実験動画
骨のミネラル密度,骨粗鬆症,骨粗鬆性骨折:全ゲノム関連研究
J B Richards1, F Rivadeneira, M Inouye
1Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Lancet (London, England)
|May 6, 2008
まとめ
LRP5 と TNFRSF11B に近い2つの遺伝子変異は,骨粗鬆症のリスクを大幅に増加させます. これらの一般的な遺伝的要因は,骨密度低下と骨折リスクに寄与し,人口のスクリーニングの可能性を示唆しています.
科学分野:
- 遺伝学 遺伝学とは
- 骨の生物学 骨の生物学
- 骨粗鬆症の研究について
背景:
- 骨粗鬆症の診断は,骨のミネラル密度 (BMD) の測定に依存しています.
- BMDは遺伝学と環境要因の影響を受ける複雑な特徴です.
- 骨粗鬆症の遺伝的決定因子を特定することは,骨粗鬆症の病因を理解するために極めて重要です.
研究 の 目的:
- 骨のミネラル密度 (BMD) と関連した遺伝的位置を特定する.
- 特定された遺伝子変異の骨粗鬆性骨折との関連を調査する.
主な方法:
- イギリスの女性2,094人を対象に314,075個の単一ヌクレオチドポリモルフィズム (SNP) の全ゲノム関連研究 (GWAS) を実施した.
- 欧州の3つのコホートにわたる6,463人の個人に有望なSNPの複製.
- リンフォブラスト細胞系におけるアレル発現の分析.
- 2つの独立した研究から得られたデータを用いて,骨粗鬆症の骨折との関連試験.
主要な成果:
- 2つのSNP,rs4355801 (TNFRSF11Bに近い) とrs3736228 (LRP5内の) は,全ゲノムにわたるBMDと有意な関連性を示しました.
- LRP5 SNP (rs3736228) は,骨粗鬆症の骨質量低下と,骨粗鬆症の骨折および骨粗鬆症のリスクの増加と関連していました.
- TNFRSF11B (rs4355801) の近くのSNPは,BMDの減少と骨粗鬆症のリスクの増加と関連していました.
- リスクアレルは一般的であり (8557人のうち22%) BMDと骨折リスクに累積的な影響を及ぼした.
- アレル発現分析により,rs4355801リスクアレルのキャリアのTNFRSF11B発現が半減することが明らかになった.
結論:
- LRP5とTNFRSF11Bの遺伝的変異は,骨粗鬆症と骨折のリスクの増加と,BMDの低下に関連しています.
- 骨折リスクに対するこれらの共通のリスクアレルの組み合わせた効果は,環境要因に相当する,重要なものです.
- これらのリスクアレルの流行は,骨粗鬆症のスクリーニング戦略における潜在的な役割を示唆しています.
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