影响线粒体功能的遗传变异为病提供了进一步的见解
Marisa Cañadas-Garre1,2,3,4, Blanca Baños-Jaime5,6, Joaquín J Maqueda5,7,8
1Molecular Epidemiology and Public Health Research Group, Centre for Public Health,, Queen's University Belfast, Institute for Clinical Sciences A, Royal Victoria Hospital, Belfast, BT12 6BA, UK. marisacgarre@gmail.com.
BMC genomics
|June 10, 2024
概括
线粒体DNA (mtDNA) 和核编码线粒体基因 (NEMG) 的遗传变异与慢性病 (CKD) 和其进展有关,为健康和疾病提供了新的见解. 这些发现突出了可能导致CKD的遗传因素,特别是在糖尿病患者中.
科学领域:
- 遗传学和基因组学 在
- 腎臟病學 (nephrology) 是一種醫學專業.
- 线粒体生物学 线粒体生物学
背景情况:
- 慢性病 (CKD) 是一个普遍存在的全球健康问题,通常是由糖尿病驱动的.
- 虽然自体遗传变异解释了一些CKD倾向,但线粒体DNA (mtDNA) 和核编码线粒体基因 (NEMG) 的作用仍然未被充分探索.
研究的目的:
- 调查mtDNA和NEMG变异与CKD和相关特征的关联.
- 特别关注这些遗传变异在糖尿病背景中的作用.
主要方法:
- 利用来自英国生物银行 (UKB) 和UK-ROI的数据,这是1型糖尿病患者的独立队列.
- 分析了线粒体变异,单元组,NEMG和功能标志物之间的关联,如估计的淋巴细胞过率 (eGFR),血清变量和末期病 (ESKD).
主要成果:
- 在UKB中确定了14种与eGFR相关的线粒体变异.
- 线粒体单双组U,H和J与eGFR和血清变量有关;单双组H与所有血清变量有关,不论糖尿病状况如何.
- 发现NEMG (例如SLC39A13,CFL1,ACP2,ATP5G1) 与损伤和血清变量,以及SLC4A1,NUP210和MYH14与ESKD的新相关性. 在糖尿病患者中,TBC1D32-rs113987180变种增加了ESKD风险.
- 在UK-ROI中,AGXT2-rs71615838,SURF1-rs183853102和TFB1M-rs869120与糖尿病病和eGFR相关.
结论:
- 发现了新的mtDNA和NEMG变异,这些变异可能解释了CKD和表型中无法解释的遗传性.
- 证实了MT-ND5和线粒体单双组H在病中的作用,并确定了MT-ND5-rs41535848G和线粒体单双组X作为ESKD的风险因素.
- 虽然大多数关联与糖尿病无关,但NEMG显示在1型糖尿病 (T1DM) 中具有潜在的作用.
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