超出1型和2型糖尿病的ONECUT1变体:探索阿拉伯队列中的临床多样性和表观遗传关联
Mohammed Dashti1, Rasheeba Nizam1, Sumi Elsa John1
1Department of Genetics and Bioinformatics, Dasman Diabetes Institute, Kuwait City, Kuwait.
Frontiers in genetics
|November 9, 2023
概括
ONECUT1基因与各种糖尿病类型有关,包括新生儿糖尿病和2型糖尿病 (T2D). ONECUT1中的遗传变异影响胰腺β细胞功能和基因表达,突出显示了它在不同人群中糖尿病发展中的作用.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 编码肝细胞核因子6的ONECUT1基因对胰腺和肝脏发育至关重要.
- 在ONECUT1中发生的突变会损害胰腺β细胞功能,并通过转录和表观遗传机制调节内分泌发育.
- 之前的研究发现了新生儿糖尿病中的ONECUT1突变,跨越了不同种族和2型糖尿病 (T2D) 患者的变异.
研究的目的:
- 研究ONECUT1基因变异与多种人群糖尿病的关联,特别是阿拉伯人群.
- 探索已识别的ONECUT1变异对基因表达和DNA甲基化的功能影响.
- 概括ONECUT1在糖尿病临床多样性中的作用.
主要方法:
- 在T1D,MODY和T2D患者中查科威特和卡塔尔队伍的ONECUT1变异.
- 使用GTEx,NephQTL,mQTLdb和HaploReg数据库对表达定量特征局部 (eQTL) 和甲基化定量特征局部 (mQTL) 效应进行鉴定变异的分析.
- 来自MODY-X患者和健康对照的外周血液的DNA甲基化概况.
主要成果:
- 在MODY,T1D和T2D患者中发现了两种同卵性变体rs202151356_p.H33Q和rs61735385_p.P94P.
- 鉴定出 rs61735385_p.P94P 变种为 eQTL 和 mQTL,影响 ONECUT1 的表达和甲基化模式.
- 与健康个体相比,在MODY-X患者的rs61735385_p.P94P变体附近的CpG部位观察到显著的低甲基化.
结论:
- 这项研究证实了ONECUT1基因变异与各种形式的糖尿病 (包括MODY,T1D和T2D) 的关联,跨越了各种种族群体.
- ONECUT1变种影响基因表达和DNA甲基化,有助于糖尿病的发病.
- 这些发现概括了ONECUT1在糖尿病临床谱中的参与.
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