Association of missense mutations in the mitochondrial MT-CO1 gene with Primary Open-Angle Glaucoma (POAG) in African-Americans.

Abstract

Purpose : To determine whether common missense variants in the mitochondrial cytochrome c oxidase subunit I gene (MT-CO1) are linked to increased glaucoma susceptibility and traits in African-Americans.

Methods : 2,367 African-American subjects, recruited from the Scheie Eye Institute and research affiliates in Philadelphia for the POAAGG study, were included. Glaucoma cases were defined by demonstrating characteristic optic nerve defects with corresponding visual field loss. Genomic DNAs were extracted from whole blood, an N-terminal fragment of the MT-CO1 gene was amplified by PCR and Sanger sequenced. Masked genotype/phenotype analyses of POAG patients with and without MT-CO1 mutations were completed.

Results : The POAG case group was significantly enriched for two disease-associated missense variants, which define a common African mitochondrial haplogroup. POAG cases harboring these variants had worse disease at significantly lower intraocular pressure than non-missense cases, after matching for age, gender, family history of POAG, and mitochondrial ancestry

Conclusions : Mitochondrial lineages that harbor missense mutations in MT-CO1 may further elevate some African-Americans already high risk for glaucoma and result in worse disease. Functional characterization of these missense variants could yield insight into the etiology of this subset of POAG patients. Mitochondrial sequence analysis has the potential to inform screening efforts and to personalize treatment, by identifying those glaucoma patients who might benefit from dietary supplementation or from other interventions designed to support mitochondrial function.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.