The atrial natriuretic peptide gene in patients with familial primary open-angle glaucoma.

Family history is a major risk factor in the development of primary open-angle glaucoma. The atrial natriuretic peptide system has been implicated in the underlying pathophysiology of the disease. This study looked for any alterations in the ANP gene and 5' proximal promoter regions of the ANP gene, in 53 patients from familial primary open-angle glaucoma families. The ANP gene was amplified by a long-PCR technique from peripheral blood DNA. Gross insertions or deletions in the gene were sought and allelic frequencies at two restriction fragment length polymorphism (RFLP) sites within the gene (Sca I, Hpa II) were compared with allelic frequencies obtained from 60 normal controls with no known family history of glaucoma or ocular hypertension. PCR-based single strand conformation polymorphism analysis was then used to search for possible point mutations in the 5' proximal promoter region of the ANP gene, which is known to contain regulatory elements which modify gene transcription. No gross alterations in the ANP gene or differences in allelic frequencies at the RFLP sites within the gene were observed. PCR-SSCP analysis of the 5' proximal promoter region of the gene revealed mutations in 10 patients in the -595 to -384bp region (19% of patients). Mutations in the 5' proximal promoter region of the ANP gene may contribute to altered ANP transcription in at least a proportion of patients with familial glaucoma.