Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle Glaucoma

Invest Ophthalmol Vis Sci. 2018 Sep 4;59(11):4598-4602. doi: 10.1167/iovs.18-25085.

Abstract

Purpose: To determine whether mitochondrial DNA haplogroups or rare variants associate with primary open-angle glaucoma in subjects of European descent.

Methods: A case-control comparison of age- and sex-matched cohorts of 90 primary open-angle glaucoma patients and 95 population controls. Full mitochondrial DNA sequences from peripheral blood were generated by next-generation sequencing and compared to the revised Cambridge Reference Sequence to define mitochondrial haplogroups and variants.

Results: Most subjects were of the major European haplogroups H, J, K, U, and T. Logistic regression analysis showed haplogroup U to be significantly underrepresented in male primary open-angle glaucoma subjects (odds ratio 0.25; 95% confidence interval [CI] 0.09-0.67; P = 0.007; Bonferroni multiple testing P = 0.022). Variants in the mitochondrial DNA gene MT-ND2 were overrepresented in the control group (P = 0.005; Bonferroni multiple testing correction P = 0.015).

Conclusions: Mitochondrial DNA ancestral lineages modulate the risk for primary open-angle glaucoma in populations of European descent. Haplogroup U and rare variants in the mitochondrial DNA-encoded MT-ND2 gene may be protective against primary open-angle glaucoma. Larger studies are warranted to explore haplogroup associations with disease risk in different ethnic groups and define biomarkers of primary open-angle glaucoma endophenotypes to target therapeutic strategies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • DNA, Mitochondrial / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Genes, Mitochondrial*
  • Genetic Predisposition to Disease*
  • Genetic Variation / genetics*
  • Glaucoma, Open-Angle / diagnosis
  • Glaucoma, Open-Angle / genetics*
  • Gonioscopy
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Intraocular Pressure
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • NADH Dehydrogenase / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic

Substances

  • DNA, Mitochondrial
  • NADH Dehydrogenase
  • MT-ND2 protein, human