Association of mitochondrial DNA variation with high myopia in a Han Chinese population

Abstract

High myopia (HM), which is characterized by oxidative stress, is one of the leading causes of visual impairment and blindness across the world. Family and population genetic studies have uncovered nuclear-genome variants in proteins functioned in the mitochondria. However, whether mitochondrial DNA mutations are involved in HM remains unexplored. Here, we performed the first large-scale whole-mitochondrial genome study in 9613 HM cases and 9606 control subjects of Han Chinese ancestry for identifying HM-associated mitochondrial variants. The single-variant association analysis identified nine novel genetic variants associated with HM reaching the entire mitochondrial wide significance level, including rs370378529 in ND2 with an odds ratio (OR) of 5.25. Interestingly, eight out of nine variants were predominantly located in related sub-haplogroups, i.e. m.5261G > A in B4b1c, m.12280A > G in G2a4, m.7912G > A in D4a3b, m.94G > A in D4e1, m.14857 T > C in D4e3, m.14280A > G in D5a2, m.16272A > G in G2a4, m.8718A > G in M71 and F1a3, indicating that the sub-haplogroup background can increase the susceptible risk for high myopia. The polygenic risk score analysis of the target and validation cohorts indicated a high accuracy for predicting HM with mtDNA variants (AUC = 0.641). Cumulatively, our findings highlight the critical roles of mitochondrial variants in untangling the genetic etiology of HM.

Lipid Metabolism Regulators Are the Possible Determinant for Characteristics of Myopic Human Scleral Stroma Fibroblasts (HSSFs)

“…Considering the fact that numerous transcription factors and coactivators, including SREBP, PGC-1α and others, are involved in regulation of the expression of enzymes catalyzing the rate-limiting steps of liver glycolytic metabolic processes [ 55 ], it is reasonable to speculate that SREBP-related mechanisms may also induce alterations in both OCR and ECAR indices among HSSF cells obtained from eyes with various ALs, as shown in Figure 1 . To support our current evidence, it is shown that high myopia may be induced by oxidative stress base upon family and population genetic studies identifying the nuclear-genome variants within proteins related to mitochondrial function rationally suggesting the critical roles of mitochondrial variants in the molecular etiology of high myopia [ 56 ].…”