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Human genetics of diabetic vascular complications

机译:糖尿病血管并发症的人类遗传学

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Diabetic vascular complications (DVC) affecting several important organ systems of human body such as the cardiovascular system constitute a major public health problem. There is evidence demonstrating that genetic factors contribute to the risk of DVC genetic variants, structural variants, and epigenetic changes play important roles in the development of DVC. Genetic linkage studies have uncovered a number of genetic loci that may shape the risk of DVC. Genetic association studies have identified many common genetic variants for susceptibility to DVC. Structural variants such as copy number variation and interactions of gene ?— environment have also been detected by association analysis. Apart from the nuclear genome, mitochondrial DNA plays a critical role in regulation of development of DVC. Epigenetic studies have indicated epigenetic changes in chromatin affecting gene transcription in response to environmental stimuli, which provided a large body of evidence of regulating development of diabetes mellitus. Recently, a new window has opened on identifying rare and common genetic loci through next generation sequencing technologies. This review focusses on the current knowledge of the genetic and epigenetic basis of DVC. Ultimately, identification of genes or genetic loci, structural variants and epigenetic changes contributing to risk of or protection from DVC will help uncover the complex mechanism(s) underlying DVC, with crucial implications for the development of personalized medicine for diabetes mellitus and its complications.
机译:影响人体几个重要器官系统(例如心血管系统)的糖尿病血管并发症(DVC)构成了主要的公共卫生问题。有证据表明,遗传因素会导致DVC遗传变异,结构变异和表观遗传变化在DVC的发展中发挥重要作用。遗传连锁研究发现了许多可能影响DVC风险的遗传基因座。遗传关联研究已经确定了许多常见的DVC易感性遗传变异。还通过关联分析检测到了结构变异,例如拷贝数变异和基因与环境的相互作用。除核基因组外,线粒体DNA在调节DVC的发育中起关键作用。表观遗传学研究表明,染色质的表观遗传学变化会响应环境刺激而影响基因转录,这为调节糖尿病的发展提供了大量证据。最近,通过下一代测序技术鉴定稀有和常见遗传基因座的新窗口已经打开。这篇综述着重于DVC的遗传和表观遗传基础的当前知识。最终,识别导致DVC风险或受到DVC保护的基因或遗传基因座,结构变异和表观遗传变化将有助于揭示DVC的复杂机制,这对于开发针对糖尿病及其并发症的个性化药物至关重要。

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