ビタミンD欠乏症の共通遺伝的決定因子:全ゲノム関連研究
Thomas J Wang1, Feng Zhang, J Brent Richards
1Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA. tjwang@partners.org
Lancet (London, England)
|June 15, 2010
まとめ
遺伝的変異はビタミンDレベルに大きく影響し,ビタミンD欠乏症のリスクを高めます. この研究では,ヨーロッパの大きな集団におけるビタミンDの状態に影響を与える重要な遺伝的位置を特定しました.
科学分野:
- 人間の遺伝学 人間の遺伝学
- 栄養バイオケミストリー
- 分子伝染病学 分子伝染病学
背景:
- ビタミンDは骨の健康に不可欠であり,骨外組織に作用します.
- 循環中の25-ヒドロキシビタミンD濃度は,日光照射,食事,遺伝子の影響を受けます.
- 遺伝的要因は,遺伝性の高いため,ビタミンDの状態に大きく寄与することが示唆されています.
研究 の 目的:
- 循環中の25-ヒドロキシビタミンD濃度に関連する一般的な遺伝子変異を特定する.
- 特定された遺伝子変異とビタミンD欠乏症のリスクとの関係を調査する.
- 全ゲノム関連研究 (GWAS) を活用して,包括的な遺伝子発見を図る.
主な方法:
- ゲノム・ワイド・アソシエーション・スタディ (GWAS) は,ヨーロッパ出身の33,996人を対象に,15コホートで実施した.
- 強力な検証のために,発見,in-silicoレプリケーション,de-novoレプリケーションコホートを活用しました.
- 25-ヒドロキシビタミンD濃度は,さまざまな測定法 (放射性免疫測定法,ELISA,質量スペクトロメトリー) を用いて測定され,不十分な値 (75 nmol/Lまたは50 nmol/L) が定義されています.
- 組み合わせられた結果のためのZスコア加重メタ解析と,確認された変異種のための構築されたゲノタイプスコアを使用しました.
主要な成果:
- 25ヒドロキシビタミンD濃度に関連した3つのロシ (4p12 GCの近く,11q12 DHCR7の近く,11p15 CYP2R1の近く) で有意な変異を特定しました.
- プーリングされたサンプルでは,追加のロカス (20q13 near CYP24A1) が全ゲノムの有意性に達した.
- 複合遺伝子型スコアの最高四分の一の個体では,ビタミンD欠乏症のリスクが著しく増加しました (OR 2.47 for <75 nmol/L, OR 1.92 for <50 nmol/L).
結論:
- コレステロール合成,水酸化,ビタミンD輸送に関与する遺伝子の近くの遺伝子変異は,ビタミンDの状態に影響します.
- これらの特定された遺伝的位置は,ビタミンDの代謝と状態を理解するために不可欠です.
- これらの位置における遺伝的変異は,ビタミンD欠乏症のリスクがかなり高い個人を効果的に特定します.
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