白种人胰岛素与脂蛋白(a)水平之间的因果关系:孟德尔随机研究。

IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Mateusz Lejawa, Marcin Goławski, Martyna Fronczek, Tadeusz Osadnik, Francesco Paneni, Massimiliano Ruscica, Natalia Pawlas, Małgorzata Lisik, Maciej Banach
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引用次数: 0

摘要

背景:大量观察性研究表明,循环中的脂蛋白(a)[Lp(a)]可能与罹患 2 型糖尿病(T2D)的风险成反比。然而,最近的孟德尔随机化(MR)研究并不一致地支持这种关联。体外研究结果表明,高浓度胰岛素可通过影响载脂蛋白(a)[apo(a)]的合成来抑制脂蛋白(a)水平。本研究旨在确定基因预测的胰岛素浓度与脂蛋白(a)水平之间的关系,这可能部分解释了低脂蛋白(a)水平与T2D风险增加之间的关联:从欧洲人群全基因组关联研究(GWASs)的荟萃分析(N = 151,013)中确定了与空腹胰岛素水平密切相关的独立遗传变异。欧洲血统人群脂蛋白(a)的汇总数据来自英国生物库(UK Biobank)的一项全基因组关联研究(GWASs)(N = 361,194)。应用逆方差加权(IVW)方法进行了双样本汇总水平 MR 分析。采用了稳健的方法进行敏感性分析,如MR-Egger、加权中位数(WME)法、MR pleiotropy residual sum and outlier (MR-PRESSO)、leave-one-out analysis和MR Steiger:结果:基因预测的空腹胰岛素水平与脂蛋白(a)水平呈负相关(β = - 0.15,SE = 0.05,P = 0.003)。敏感性分析显示,WME(β = - 0.26,SE = 0.07,P = 0.0002)而非 MR-Egger(β = - 0.22,SE = 0.13,P = 0.11)支持遗传易感性胰岛素水平与脂蛋白(a)之间的因果关系:我们的磁共振研究提供了强有力的证据,支持遗传预测的胰岛素浓度升高与脂蛋白(a)浓度降低之间的关联。这些研究结果表明,高胰岛素血症通常伴随着终末期糖尿病,它可以部分解释低脂蛋白(a)浓度与终末期糖尿病风险增加之间的反向关系。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Causal associations between insulin and Lp(a) levels in Caucasian population: a Mendelian randomization study.

Background: Numerous observational studies have demonstrated that circulating lipoprotein(a) [Lp(a)] might be inversely related to the risk of type 2 diabetes (T2D). However, recent Mendelian randomization (MR) studies do not consistently support this association. The results of in vitro research suggest that high insulin concentrations can suppress Lp(a) levels by affecting apolipoprotein(a) [apo(a)] synthesis. This study aimed to identify the relationship between genetically predicted insulin concentrations and Lp(a) levels, which may partly explain the associations between low Lp(a) levels and increased risk of T2D.

Methods: Independent genetic variants strongly associated with fasting insulin levels were identified from meta-analyses of genome-wide association studies in European populations (GWASs) (N = 151,013). Summary level data for Lp(a) in the population of European ancestry were acquired from a GWAS in the UK Biobank (N = 361,194). The inverse-variance weighted (IVW) method approach was applied to perform two-sample summary-level MR. Robust methods for sensitivity analysis were utilized, such as MR‒Egger, the weighted median (WME) method, MR pleiotropy residual sum and outlier (MR-PRESSO), leave-one-out analysis, and MR Steiger.

Results: Genetically predicted fasting insulin levels were negatively associated with Lp(a) levels (β = - 0.15, SE = 0.05, P = 0.003). The sensitivity analysis revealed that WME (β = - 0.26, SE = 0.07, P = 0.0002), but not MR‒Egger (β = - 0.22, SE = 0.13, P = 0.11), supported a causal relationship between genetically predisposed insulin levels and Lp(a).

Conclusion: Our MR study provides robust evidence supporting the association between genetically predicted increased insulin concentrations and decreased concentrations of Lp(a). These findings suggest that hyperinsulinaemia, which typically accompanies T2D, can partially explain the inverse relationship between low Lp(a) concentrations and an increased risk of T2D.

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来源期刊
Cardiovascular Diabetology
Cardiovascular Diabetology 医学-内分泌学与代谢
CiteScore
12.30
自引率
15.10%
发文量
240
审稿时长
1 months
期刊介绍: Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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