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Evidence for Association of Endothelial Nitric Oxide Synthase Gene in Subjects with Glaucoma and a History of Migraine

¹From the Department of Ophthalmology, The Royal Group of Hospitals, Belfast, United Kingdom; the ²Centre for Vision Science and the ³Department of Epidemiology and Public Health, Queen’s University, Belfast, United Kingdom; and the ⁴Faculty of Biomedical Sciences, University of Ulster, Coleraine, United Kingdom.

PURPOSE. There is evidence to suggest that vasospasm and vascular dysregulation play a role in the etiology of glaucoma. This effect may be particularly relevant in patients with glaucoma who have a history of migraine or vasospastic tendencies. This study was conducted to investigate the role of genes with products that regulate blood flow to ocular tissues. The candidate genes were the two isoforms of nitric oxide synthase (NOS), NOS3 and -2A, and endothelin (ET)-l. The frequency of the T786C mutation in NOS3 was also examined.

METHODS. DNA was obtained from 58 patients with primary open-angle glaucoma (POAG), 76 with normal tension glaucoma (NTG), and 38 control subjects. Polymerase chain reactions (PCR) were used to compare the frequency of the alleles between the subjects with glaucoma and the control subjects and the subjects with glaucoma with vasospasm or migraine. The PCR product was sequenced to identify the frequency of the T786C mutation.

RESULTS. The distribution of the NOS3 repeat alleles in subjects with glaucoma and control subjects just failed to reach statistical significance (P = 0.06). The distribution in subjects with NTG or POAG did not differ significantly. A significant difference was found (P < 0.001) in the distribution of allele frequencies of the NOS3 marker in subjects who had glaucoma with migraine versus control subjects. There were no differences in the distribution of the NOS2A or ET-1 markers between the subjects with glaucoma and the control subjects.

CONCLUSIONS. This study provides evidence of an association between the NOS3 gene and subjects with glaucoma who have a history of migraine. Unlike in other studies, no evidence was found of an association between ET-1 and glaucoma.

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