Mitochondrial DNA heteroplasmy analysis in keratoconus patients from China

Liyan Xu; Kaili Yang; Qi Fan; Yuwei Gu; Shengwei Ren

doi:10.3389/fgene.2023.1251951

Mitochondrial DNA heteroplasmy analysis in keratoconus patients from China

Front Genet. 2023 Sep 18:14:1251951. doi: 10.3389/fgene.2023.1251951. eCollection 2023.

Authors

Liyan Xu¹, Kaili Yang¹, Qi Fan¹, Yuwei Gu¹, Shengwei Ren¹

Affiliation

¹ Henan Provincial People's Hospital, Henan Eye Hospital, People's Hospital of Zhengzhou University, Zhengzhou, China.

Abstract

Background: 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. Methods: 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. Results: The distribution of mtDNA heteroplasmic variants showed the highest number of heteroplasmic variants in the non-coding region, while the COX3 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 p > 0.05). In addition, the number of heteroplasmic variants was positively associated with age in all subjects (r = 0.085, p = 0.037). The logistic regression analyses indicated that the heteroplasmic levels of m.16180_16181delAA was associated with KC (p < 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 p > 0.05) in KC cases and controls separately. Conclusion: The current study characterized the mtDNA heteroplasmy profile in KC, and revealed that the heteroplasmic levels of m.16180_16181delAA were associated with KC.

Keywords: heteroplasmy; keratoconus; m.16180_16181delAA; mitochondrial DNA; variant.

Grants and funding

This research was funded by the Henan Natural Science Foundation (No. 222300420536), Special Program for Basic Research of Henan Eye Hospital (No. 20JCZD003), Henan Young Health Science and Technology Innovation Outstanding Program (No. YXKC2020023), Henan Provincial Building Key Program (No. SBGJ202002028), Henan Provincial Medical Science and Technology Joint Program (Nos. LHGJ20210080 and LHGJ20220707), Henan Provincial Scientific and Technological Research Project (Nos. 222102310307 and 222102310599), Youth Special Program for Basic Research of Henan Eye Hospital (Nos. 21JCQN006 and 21JCQN008).