低密度脂質タンパク質のコレステロールを下げる遺伝子変異と2型糖尿病のリスクとの関連:メタ解析
Luca A Lotta1, Stephen J Sharp1, Stephen Burgess2
1MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
JAMA
|October 5, 2016
まとめ
NPC1L1に近い低密度脂質タンパク質コレステロール (LDL- C) を低下させる遺伝的変異は,2型糖尿病のリスク増加と関連しています. この発見は,LDL-Cを低下させる治療の潜在的有害な代謝効果を示唆している.
科学分野:
- 遺伝学
- 代謝 疾患
- ファルマゲノミクス
背景:
- NPC1L1とHMGCRの近くの低密度脂質タンパク質コレステロール (LDL- C) 低下アレルは,エゼチミブとスタチンの有効性の代理として機能しています.
- HMGCRアレルは2型糖尿病のリスク増加と関連しており,スタチン試験の観察を反映しています.
- NPC1L1アレルと2型糖尿病のリスクとの関連は未だに確立されていません.
研究 の 目的:
- NPC1L1内またはその近くにあるLDL-Cを低下させるアレルと他の遺伝子との関連を調べる.
- これらの遺伝子変異と関連した2型糖尿病のリスクを調査する.
- 脂質低下療法による潜在的有害な代謝効果を調べる
主な方法:
- 遺伝子関連の研究のメタ分析が行われました.
- 2型糖尿病,冠動脈疾患,対照群を含む.
- データは1991年から2016年の間にヨーロッパとアメリカの人口から収集されました.
主要な成果:
- NPC1L1のLDL-Cを低下させる変種は,冠動脈疾患と逆相関を示したが,2型糖尿病と直接相関を示した.
- PCSK9の変種は,LDL- Cの減少による2型糖尿病のリスクの増加と関連していることも示された.
- 遺伝的変異によるLDL-C減少は同様に冠動脈疾患のリスクを低下させましたが,2型糖尿病の関連性は異質で遺伝子特異でした.
結論:
- 特にNPC1L1の近くにあるLDL-Cを低下させる遺伝的変異体への曝露は,2型糖尿病の高リスクと関連しています.
- これらの発見は,LDL-Cを低下させる治療の潜在的有害な代謝結果についての洞察を提供します.
- 遺伝子特異的な関連は,遺伝的脂質低下変異と関連した代謝リスクの複雑さを強調しています.
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