TRIB3 R84 变异与 2426 名白人个体样本中的左心室质量增加有关。

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

机构信息

Department of Medical and Surgical Sciences, University "Magna Graecia" of Catanzaro, Viale Europa, 88100, Catanzaro, Italy.

Department of Clinical and Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.

出版信息

Cardiovasc Diabetol. 2021 May 29;20(1):115. doi: 10.1186/s12933-021-01308-4.

DOI:10.1186/s12933-021-01308-4

PMID:34051802

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8164223/

Abstract

BACKGROUND

Prior studies in animal models showed that increased cardiac expression of TRIB3 has a pathogenic role in inducing left ventricular mass (LVM). Whether alterations in TRIB3 expression or function have a pathogenic role in inducing LVM increase also in humans is still unsettled. In order to address this issue, we took advantage of a nonsynonymous TRIB3 Q84R polymorphism (rs2295490), a gain-of-function amino acid substitution impairing insulin signalling, and action in primary human endothelial cells which has been associated with insulin resistance, and early vascular atherosclerosis.

METHODS

SNP rs2295490 was genotyped in 2426 White adults in whom LVM index (LVMI) was assessed by validated echocardiography-derived measures.

RESULTS

After adjusting for age and sex, LVMI progressively and significantly increased from 108 to 113, to 125 g/m in Q84Q, Q84R, and R84R individuals, respectively (Q84R vs. Q84Q, P = 0.03; R84R vs. Q84Q, P < 0.0001). The association between LVMI and the Q84R and R84R genotype remained significant after adjusting for blood pressure, smoking habit, fasting glucose levels, glucose tolerance status, anti-hypertensive treatments, and lipid-lowering therapy (Q84R vs. Q84Q, P = 0.01; R84R vs. Q84Q, P < 0.0001).

CONCLUSIONS

We found that the gain-of-function TRIB3 Q84R variant is significantly associated with left ventricular mass in a large sample of White nondiabetic individual of European ancestry.

摘要

背景

先前的动物模型研究表明，TRIB3 在心脏中的表达增加在诱导左心室质量（LVM）增加方面具有致病性作用。TRIB3 表达或功能的改变是否在诱导人类 LVM 增加方面也具有致病性作用仍未确定。为了解决这个问题，我们利用了一种非同义 TRIB3 Q84R 多态性（rs2295490），这是一种功能获得性氨基酸取代，会损害胰岛素信号传导，并在原发性人内皮细胞中起作用，与胰岛素抵抗和早期血管动脉粥样硬化有关。

方法

在 2426 名白人成年人中对 SNP rs2295490 进行基因分型，通过经过验证的超声心动图衍生测量评估 LVM 指数（LVMI）。

结果

在调整年龄和性别后，LVMI 逐渐显著增加，从 108 增加到 113，再增加到 125g/m，在 Q84Q、Q84R 和 R84R 个体中分别为 Q84Q、Q84R 和 R84R 个体（Q84R 与 Q84Q 相比，P=0.03；R84R 与 Q84Q 相比，P<0.0001）。在调整血压、吸烟习惯、空腹血糖水平、葡萄糖耐量状态、抗高血压治疗和降脂治疗后，LVMI 与 Q84R 和 R84R 基因型之间的关联仍然显著（Q84R 与 Q84Q 相比，P=0.01；R84R 与 Q84Q 相比，P<0.0001）。