弥合2型糖尿病的变异与功能差距:进展和挑战
Adam G Maynard1,2, Raghav Bhardwaj1,2, Thouis R Jones1,2,3
1Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Diabetologia
|November 22, 2025
概括
新的策略将遗传变异与特定的基因功能联系起来,改善我们对2型糖尿病机制的理解. 这项研究有助于弥合基因发现和精准医学的生物见解之间的差距.
科学领域:
- 遗传学 遗传学 是一个
- 代谢疾病 代谢疾病
- 分子生物学分子生物学
背景情况:
- 全球2型糖尿病患病人数超过5.3亿,预计到2050年这一数字将达到13亿.
- 全基因组关联研究确定了1200多个2型糖尿病位点,但大多数风险变体位于非编码区域,阻碍了生物解释,并解释了有限的遗传性.
研究的目的:
- 审查变异到功能 (V2F) 策略的进展,以将非编码基因变异与2型糖尿病中的分子机制联系起来.
- 突出V2F在关键2型糖尿病相关组织中的发现,并讨论准确医学的新兴工具.
主要方法:
- 精细地图的绘制.
- 染色素分析是如何分析染色素的
- 单细胞多组体的单细胞多组体.
- 可扩展的基于CRISPR的扰动策略.
- 机器学习工具 机器学习工具
主要成果:
- V2F策略开始将非编码变体与效应基因,组织和分子机制联系起来.
- 具体的例子包括胰腺β细胞中的TCF7L2,肝细胞中的SLC16A11和PNPLA3,以及脂肪细胞和肌肉中的GLUT4贩运.
- 提供了V2F发现的摘要表和新兴工具的讨论.
结论:
- 最近的V2F进展对于理解2型糖尿病遗传风险的生物学基础至关重要.
- 这些发展对于解决疾病异质性和为精准医学方法铺平道路至关重要.
相关概念视频
Diabetes Mellitus: Overview and Type I Subtype
4.8K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
4.8K
Diabetes Mellitus: Type 2 and Gestational
4.3K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
4.3K
Carbohydrate Metabolism
13.7K
Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
13.7K
Diabetes: Management and Pharmacotherapy
851
The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
851
Pathophysiology of Diabetes
3.1K
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
3.1K
Diabetes: Symptoms, Diagnosis, and Complications
2.0K
For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is...
2.0K


