Mitochondrial DNA variation and disease susceptibility in primary open-angle glaucoma

Larry N. Singh, Jonathan G. Crowston, M. Isabel G. Lopez Sanchez, Nicole J. Van Bergen, Lisa S. Kearns, Alex W. Hewitt, Seyhan Yazar, David A. Mackey, Douglas C. Wallace, Ian A. Trounce

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)4598-4602
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number11
DOIs
Publication statusPublished - 1 Sep 2018

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Mitochondrial Diseases
Disease Susceptibility
Mitochondrial DNA
Endophenotypes
Mitochondrial Genes
Population Control
Ethnic Groups
Primary Open Angle Glaucoma
Biomarkers
Logistic Models
Odds Ratio
Regression Analysis
Confidence Intervals
Control Groups
Population
Genes

Cite this

Singh, L. N., Crowston, J. G., Lopez Sanchez, M. I. G., Van Bergen, N. J., Kearns, L. S., Hewitt, A. W., ... Trounce, I. A. (2018). Mitochondrial DNA variation and disease susceptibility in primary open-angle glaucoma. Investigative Ophthalmology and Visual Science, 59(11), 4598-4602. https://doi.org/10.1167/iovs.18-25085
Singh, Larry N. ; Crowston, Jonathan G. ; Lopez Sanchez, M. Isabel G. ; Van Bergen, Nicole J. ; Kearns, Lisa S. ; Hewitt, Alex W. ; Yazar, Seyhan ; Mackey, David A. ; Wallace, Douglas C. ; Trounce, Ian A. / Mitochondrial DNA variation and disease susceptibility in primary open-angle glaucoma. In: Investigative Ophthalmology and Visual Science. 2018 ; Vol. 59, No. 11. pp. 4598-4602.
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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.",
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Singh, LN, Crowston, JG, Lopez Sanchez, MIG, Van Bergen, NJ, Kearns, LS, Hewitt, AW, Yazar, S, Mackey, DA, Wallace, DC & Trounce, IA 2018, 'Mitochondrial DNA variation and disease susceptibility in primary open-angle glaucoma' Investigative Ophthalmology and Visual Science, vol. 59, no. 11, pp. 4598-4602. https://doi.org/10.1167/iovs.18-25085

Mitochondrial DNA variation and disease susceptibility in primary open-angle glaucoma. / Singh, Larry N.; Crowston, Jonathan G.; Lopez Sanchez, M. Isabel G.; Van Bergen, Nicole J.; Kearns, Lisa S.; Hewitt, Alex W.; Yazar, Seyhan; Mackey, David A.; Wallace, Douglas C.; Trounce, Ian A.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 11, 01.09.2018, p. 4598-4602.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mitochondrial DNA variation and disease susceptibility in primary open-angle glaucoma

AU - Singh, Larry N.

AU - Crowston, Jonathan G.

AU - Lopez Sanchez, M. Isabel G.

AU - Van Bergen, Nicole J.

AU - Kearns, Lisa S.

AU - Hewitt, Alex W.

AU - Yazar, Seyhan

AU - Mackey, David A.

AU - Wallace, Douglas C.

AU - Trounce, Ian A.

PY - 2018/9/1

Y1 - 2018/9/1

N2 - 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.

AB - 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.

KW - Glaucoma

KW - Haplogroup

KW - Mitochondrial DNA (mtDNA)

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