Xu Liyan, Yang Kaili, Fan Qi, Gu Yuwei, Ren Shengwei
Henan Provincial People's Hospital, Henan Eye Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.
Front Genet. 2023 Sep 18;14:1251951. doi: 10.3389/fgene.2023.1251951. eCollection 2023.
Mitochondrial DNA (mtDNA) variants have been implicated in keratoconus (KC). The present study aimed to characterize the mtDNA heteroplasmy profile in KC and explore the association of mitochondrial heteroplasmic levels with KC. Mitochondrial sequencing of peripheral blood samples and corneal tomography were conducted in 300 KC cases and 300 matched controls. The number of heteroplasmic and homoplasmic variants was calculated across the mitochondrial genome. Spearman's correlation was used to analyze the correlation between the number of heteroplasmic variants and age. The association of mtDNA heteroplasmic level with KC was analyzed by logistic regression analysis. Moreover, the relationship between mitochondrial heteroplasmic levels and clinical parameters was determined by linear regression analysis. The distribution of mtDNA heteroplasmic variants showed the highest number of heteroplasmic variants in the non-coding region, while the gene exhibited the highest number in protein-coding genes. Comparisons of the number of heteroplasmic and homoplasmic non-synonymous variants in protein-coding genes revealed no significant differences between KC cases and controls (all > 0.05). In addition, the number of heteroplasmic variants was positively associated with age in all subjects ( = 0.085, = 0.037). The logistic regression analyses indicated that the heteroplasmic levels of m.16180_16181delAA was associated with KC ( < 0.005). Linear regression analyses demonstrated that the heteroplasmic levels of m.16180_16181delAA and m.302A>C were not correlated with thinnest corneal thickness (TCT), steep keratometry (Ks), and flat keratometry (Kf) (all > 0.05) in KC cases and controls separately. The current study characterized the mtDNA heteroplasmy profile in KC, and revealed that the heteroplasmic levels of m.16180_16181delAA were associated with KC.
线粒体DNA（mtDNA）变异与圆锥角膜（KC）有关。本研究旨在描述KC患者的mtDNA异质性图谱，并探讨线粒体异质水平与KC的关联。对300例KC患者和300例匹配对照进行外周血样本的线粒体测序和角膜地形图检查。计算整个线粒体基因组中的异质和同质变异数量。采用Spearman相关性分析异质变异数量与年龄之间的相关性。通过逻辑回归分析mtDNA异质水平与KC的关联。此外，通过线性回归分析确定线粒体异质水平与临床参数之间的关系。mtDNA异质变异的分布显示非编码区的异质变异数量最多，而蛋白质编码基因中的基因数量最多。蛋白质编码基因中异质和同质非同义变异数量的比较显示，KC患者和对照之间无显著差异（均>0.05）。此外，所有受试者中异质变异数量与年龄呈正相关（=0.085，=0.037）。逻辑回归分析表明，m.16180_16181delAA的异质水平与KC有关（<0.005）。线性回归分析表明，在KC患者和对照中，m.16180_16181delAA和m.302A>C的异质水平与最薄角膜厚度（TCT）、陡峭角膜曲率（Ks）和平坦角膜曲率（Kf）均无相关性（均>0.05）。本研究描述了KC患者的mtDNA异质性图谱，并揭示m.16180_16181delAA的异质水平与KC有关。
