• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

该基因在心脏中的表达水平与心脏和葡萄糖代谢相关表型及功能途径高度相关。

Expression Levels of the Gene in the Heart Are Highly Associated with Cardiac and Glucose Metabolism-Related Phenotypes and Functional Pathways.

机构信息

Department of Cardiology, Affiliated Hospital of Nantong University, Nantong 226001, China.

Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

出版信息

Int J Mol Sci. 2023 Aug 14;24(16):12759. doi: 10.3390/ijms241612759.

DOI:10.3390/ijms241612759
PMID:37628941
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10454158/
Abstract

BACKGROUND

Troponin-I interacting kinase encoded by the gene is expressed in nuclei and Z-discs of cardiomyocytes. Mutations in were identified in patients with cardiac conduction diseases, arrhythmias, and cardiomyopathy.

METHODS

We performed cardiac gene expression, whole genome sequencing (WGS), and cardiac function analysis in 40 strains of BXD recombinant inbred mice derived from C57BL/6J (B6) and DBA/2J (D2) strains. Expression quantitative trait loci (eQTLs) mapping and gene enrichment analysis was performed, followed by validation of candidate -regulatory genes.

RESULTS

WGS identified compound splicing and missense T659I variants in the D2 parent and some BXD strains (D allele) and these strains had significantly lower expression than those carrying wild-type (B allele). Expression levels of significantly correlated with multiple cardiac (heart rate, wall thickness, PR duration, and T amplitude) and metabolic (glucose levels and insulin resistance) phenotypes in BXDs. A significant -eQTL on chromosome 3 was identified for the regulation of expression. Furthermore, -correlated genes were primarily involved in cardiac and glucose metabolism-related functions and pathways. Genes , , , , , , , , , , , and were differentially expressed between the B and D alleles.

CONCLUSIONS

Compound splicing and T659I variants reduce cardiac expression and levels are associated with cardiac and glucose metabolism-related phenotypes.

摘要

背景

基因编码的肌钙蛋白 I 相互作用激酶在心肌细胞的核和 Z 盘表达。在患有心脏传导疾病、心律失常和心肌病的患者中发现了基因突变。

方法

我们对来自 C57BL/6J（B6）和 DBA/2J（D2）品系的 40 个 BXD 重组近交系小鼠进行了心脏基因表达、全基因组测序（WGS）和心脏功能分析。进行了表达数量性状基因座（eQTL）图谱和基因富集分析，随后对候选 - 调节基因进行了验证。

结果

WGS 在 D2 亲本和一些 BXD 株系（D 等位基因）中鉴定出复合剪接和错义 T659I 变异，这些株系的表达水平明显低于携带野生型（B 等位基因）的。在 BXDs 中，的表达水平与多个心脏（心率、壁厚度、PR 间期和 T 波幅度）和代谢（血糖水平和胰岛素抵抗）表型显著相关。在 3 号染色体上确定了一个显著的 -eQTL，用于调节的表达。此外，-相关基因主要参与心脏和葡萄糖代谢相关功能和途径。基因、、、、、、、、、和在 B 和 D 等位基因之间表达差异。

结论

复合剪接和 T659I 变异降低了心脏的表达，水平与心脏和葡萄糖代谢相关表型相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/c79debb31515/ijms-24-12759-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/3b347dc8d8a0/ijms-24-12759-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/bc97ddd84086/ijms-24-12759-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/e4a7d6ca666b/ijms-24-12759-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/abff0601a3f1/ijms-24-12759-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/3b5d7305b295/ijms-24-12759-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/ec3ca220740f/ijms-24-12759-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/a6bd3a8725fa/ijms-24-12759-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/c79debb31515/ijms-24-12759-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/3b347dc8d8a0/ijms-24-12759-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/bc97ddd84086/ijms-24-12759-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/e4a7d6ca666b/ijms-24-12759-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/abff0601a3f1/ijms-24-12759-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/3b5d7305b295/ijms-24-12759-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/ec3ca220740f/ijms-24-12759-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/a6bd3a8725fa/ijms-24-12759-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ae/10454158/c79debb31515/ijms-24-12759-g008.jpg

相似文献

1
Expression Levels of the Gene in the Heart Are Highly Associated with Cardiac and Glucose Metabolism-Related Phenotypes and Functional Pathways.该基因在心脏中的表达水平与心脏和葡萄糖代谢相关表型及功能途径高度相关。
Int J Mol Sci. 2023 Aug 14;24(16):12759. doi: 10.3390/ijms241612759.
2
Dissection of a quantitative trait locus for PR interval duration identifies Tnni3k as a novel modulator of cardiac conduction.解析 PR 间期持续时间的数量性状位点，鉴定 Tnni3k 为心脏传导的新型调节剂。
PLoS Genet. 2012;8(12):e1003113. doi: 10.1371/journal.pgen.1003113. Epub 2012 Dec 6.
3
Echocardiography phenotyping in murine genetic reference population of BXD strains reveals significant QTLs associated with cardiac function and morphology.在 BXD 品系的小鼠遗传参考群体中进行超声心动图表型分析揭示了与心脏功能和形态相关的重要 QTL。
Physiol Genomics. 2023 Feb 1;55(2):51-66. doi: 10.1152/physiolgenomics.00120.2022. Epub 2022 Dec 19.
4
Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.心肌肌钙蛋白 I 相互作用激酶影响心肌细胞 S 期活性，但不影响心肌细胞增殖。
Circulation. 2023 Jan 10;147(2):142-153. doi: 10.1161/CIRCULATIONAHA.122.061130. Epub 2022 Nov 16.
5
The abundance of cis-acting loci leading to differential allele expression in F1 mice and their relationship to loci harboring genes affecting complex traits.导致F1小鼠中差异等位基因表达的顺式作用位点的丰度及其与携带影响复杂性状基因的位点的关系。
BMC Genomics. 2016 Aug 11;17(1):620. doi: 10.1186/s12864-016-2922-9.
6
The prevalent I686T human variant and loss-of-function mutations in the cardiomyocyte-specific kinase gene TNNI3K cause adverse contractility and concentric remodeling in mice.心肌细胞特异性激酶基因TNNI3K中普遍存在的I686T人类变体和功能丧失突变会导致小鼠出现不良收缩性和向心性重塑。
Hum Mol Genet. 2021 Jan 6;29(21):3504-3515. doi: 10.1093/hmg/ddaa234.
7
Genetic Burden of in Diagnostic Testing of Patients With Dilated Cardiomyopathy and Supraventricular Arrhythmias.扩张型心肌病和室上性心律失常患者诊断检测中的遗传负担。
Circ Genom Precis Med. 2023 Aug;16(4):328-336. doi: 10.1161/CIRCGEN.122.003975. Epub 2023 May 18.
8
Tnni3k alleles influence ventricular mononuclear diploid cardiomyocyte frequency.Tnni3k 等位基因影响心室单核二倍体心肌细胞的频率。
PLoS Genet. 2019 Oct 7;15(10):e1008354. doi: 10.1371/journal.pgen.1008354. eCollection 2019 Oct.
9
Overexpression of TNNI3K, a cardiac-specific MAPKKK, promotes cardiac dysfunction.心肌特异性 MAPKKK TNNI3K 的过表达可导致心脏功能障碍。
J Mol Cell Cardiol. 2013 Jan;54:101-11. doi: 10.1016/j.yjmcc.2012.10.004. Epub 2012 Oct 16.
10
Exploring the Regulation and Function of in the Development of Early-Onset Dilated Cardiomyopathy and Congestive Heart Failure Using Systems Genetics Approach.采用系统遗传学方法研究在早发性扩张型心肌病和充血性心力衰竭发展中的调控和功能。
Genes (Basel). 2023 Dec 29;15(1):53. doi: 10.3390/genes15010053.

引用本文的文献

1
Unraveling the genetic blueprint of doxorubicin-induced cardiotoxicity through systems genetics approaches.通过系统遗传学方法解析阿霉素诱导的心脏毒性的遗传蓝图。
Cardiooncology. 2025 Jun 3;11(1):53. doi: 10.1186/s40959-025-00349-y.
2
Unraveling the Genetic Blueprint of Doxorubicin-Induced Cardiotoxicity Through Systems Genetics Approaches.通过系统遗传学方法解析阿霉素诱导的心脏毒性的遗传蓝图。
Res Sq. 2025 Apr 15:rs.3.rs-6224399. doi: 10.21203/rs.3.rs-6224399/v1.
3
Genetic Adaptations of the Tibetan Pig to High-Altitude Hypoxia on the Qinghai-Tibet Plateau.

本文引用的文献

1
The S358L mutation affects cardiac, small intestine, and metabolic homeostasis in a knock-in mouse model.S358L 突变影响 knock-in 小鼠模型中心脏、小肠和代谢稳态。
Am J Physiol Heart Circ Physiol. 2023 Jun 1;324(6):H866-H880. doi: 10.1152/ajpheart.00712.2022. Epub 2023 Apr 21.
2
Echocardiography phenotyping in murine genetic reference population of BXD strains reveals significant QTLs associated with cardiac function and morphology.在 BXD 品系的小鼠遗传参考群体中进行超声心动图表型分析揭示了与心脏功能和形态相关的重要 QTL。
Physiol Genomics. 2023 Feb 1;55(2):51-66. doi: 10.1152/physiolgenomics.00120.2022. Epub 2022 Dec 19.
3
藏猪对青藏高原高寒缺氧的遗传适应。
Int J Mol Sci. 2024 Oct 21;25(20):11303. doi: 10.3390/ijms252011303.
4
Molecular Pathways and Animal Models of Cardiomyopathies.心肌疾病的分子途径和动物模型。
Adv Exp Med Biol. 2024;1441:991-1019. doi: 10.1007/978-3-031-44087-8_64.
Cardiac Troponin I-Interacting Kinase Affects Cardiomyocyte S-Phase Activity but Not Cardiomyocyte Proliferation.
心肌肌钙蛋白 I 相互作用激酶影响心肌细胞 S 期活性，但不影响心肌细胞增殖。
Circulation. 2023 Jan 10;147(2):142-153. doi: 10.1161/CIRCULATIONAHA.122.061130. Epub 2022 Nov 16.
4
Whole-Exome Sequencing Identifies a Novel Variant (c.1538T > C) of in Arrhythmogenic Right Ventricular Cardiomyopathy.全外显子组测序鉴定出致心律失常性右室心肌病中一种新的（c.1538T > C）变异。
Front Cardiovasc Med. 2022 Feb 22;9:843837. doi: 10.3389/fcvm.2022.843837. eCollection 2022.
5
Systems genetics analysis defines importance of TMEM43/ for cardiac- and metabolic-related pathways.系统遗传学分析定义了 TMEM43/在心脏和代谢相关通路中的重要性。
Physiol Genomics. 2022 Jan 1;54(1):22-35. doi: 10.1152/physiolgenomics.00066.2021. Epub 2021 Nov 12.
6
The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment.TNNI3K 在心脏疾病中的多种作用及治疗潜力。
Int J Mol Sci. 2021 Jun 15;22(12):6422. doi: 10.3390/ijms22126422.
7
The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets.2021 年的 STRING 数据库：可定制的蛋白质-蛋白质网络，以及用户上传的基因/测量集的功能特征分析。
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612. doi: 10.1093/nar/gkaa1074.
8
The role of Smad signaling cascades in cardiac fibrosis.Smad 信号级联在心脏纤维化中的作用。
Cell Signal. 2021 Jan;77:109826. doi: 10.1016/j.cellsig.2020.109826. Epub 2020 Nov 5.
9
The mutational constraint spectrum quantified from variation in 141,456 humans.从 141456 名人类个体的变异中量化的突变约束谱。
Nature. 2020 May;581(7809):434-443. doi: 10.1038/s41586-020-2308-7. Epub 2020 May 27.
10
Systematic comparison of the protein-protein interaction databases from a user's perspective.从用户角度对蛋白质-蛋白质相互作用数据库进行系统比较。
J Biomed Inform. 2020 Mar;103:103380. doi: 10.1016/j.jbi.2020.103380. Epub 2020 Jan 28.