4.7 Article

New Insights Into Mitochondrial Dysfunction at Disease Susceptibility Loci in the Development of Type 2 Diabetes

期刊

FRONTIERS IN ENDOCRINOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fendo.2021.694893

关键词

mitochondrial dysfunction; type 2 diabetes; insulin action and resistance; adipose tissue; gene set enrichment analyses; differential gene expression; heritable susceptibility

资金

  1. Medical Research Council, United Kingdom [91993]
  2. Wellcome Trust, United Kingdom [209106/Z/17/Z]
  3. Wellcome Trust [209106/Z/17/Z] Funding Source: Wellcome Trust

向作者/读者索取更多资源

This study identified potential genetic mechanisms underlying adipose tissue mitochondrial dysfunction in Type 2 diabetes by analyzing nuclear-encoded mitochondrial genes (NEMGs) regulated by T2D-associated genetic loci. Among the 763 cis-genes associated with T2D-eQTL, 50 were NEMGs, showing differential expression and association with mapped T2D disease loci.
This study investigated the potential genetic mechanisms which underlie adipose tissue mitochondrial dysfunction in Type 2 diabetes (T2D), by systematically identifying nuclear-encoded mitochondrial genes (NEMGs) among the genes regulated by T2D-associated genetic loci. The target genes of these 'disease loci' were identified by mapping genetic loci associated with both disease and gene expression levels (expression quantitative trait loci, eQTL) using high resolution genetic maps, with independent estimates co-locating to within a small genetic distance. These co-locating signals were defined as T2D-eQTL and the target genes as T2D cis-genes. In total, 763 cis-genes were associated with T2D-eQTL, of which 50 were NEMGs. Independent gene expression datasets for T2D and insulin resistant cases and controls confirmed that the cis-genes and cis-NEMGs were enriched for differential expression in cases, providing independent validation that genetic maps can identify informative functional genes. Two additional results were consistent with a potential role of T2D-eQTL in regulating the 50 identified cis-NEMGs in the context of T2D risk: (1) the 50 cis-NEMGs showed greater differential expression compared to other NEMGs and (2) other NEMGs showed a trend towards significantly decreased expression if their expression levels correlated more highly with the subset of 50 cis-NEMGs. These 50 cis-NEMGs, which are differentially expressed and associated with mapped T2D disease loci, encode proteins acting within key mitochondrial pathways, including some of current therapeutic interest such as the metabolism of branched-chain amino acids, GABA and biotin.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据