This website uses cookies to help us give you the best browsing experience. By continuing to use this portal, you agree to our use of this tool.
To learn more about how we use cookies and how to manage them please read our notice here.
Journal Club
Experimental Paper of the Month - Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle Glaucoma
Mitochondrial DNA Variation and Disease Susceptibility in Primary Open-Angle Glaucoma

Publishing date: November 2018

Author(s): Singh LN (1), Crowston JG (2), Lopez Sanchez MIG (2), Van Bergen NJ (2), Kearns LS (2), Hewitt AW (2,3), Yazar S (4,5), Mackey DA (4), Wallace DC (1,6), Trounce IA (2)

1 Center for Mitochondrial and Epigenomic Medicine, Children's Hospital of Philadelphia Research Institute, University of Pennsylvania, Philadelphia, United States.
2 Center for Eye Research Australia, Ophthalmology, University of Melbourne Department of Surgery, Melbourne, Australia.
3 Menzies Research Institute Tasmania, School of Medicine, University of Tasmania, Hobart, Australia.
4 Lions Eye Institute, University of Western Australia, Centre for Ophthalmology and Visual Science, Perth, Australia.
5 MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
6 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, United States.

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 http://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.

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


Experimental Paper of the Month manager: Andreas Boehm

back to top