THE ATRIAL-NATRIURETIC-PEPTIDE GENE IN PATIENTS WITH FAMILIAL PRIMARYOPEN-ANGLE GLAUCOMA

Family history is a major risk factor in the development of primary op en-angle glaucoma. The atrial natriuretic peptide system has been impl icated in the underlying pathophysiology of the disease, This study lo oked for any alterations in the ANP gene and 5' proximal promoter regi ons of the ANP gene, in 53 patients from familial primary open-angle g laucoma families. The ANP gene was amplified by a long-PCR technique f rom peripheral blood DNA. Gross insertions or deletions in the gene we re sought and allelic frequencies at two restriction fragment length p olymorphism (RFLP) sites within the gene (Sea I, Hpa II) were compared with allelic frequencies obtained from 60 normal controls with no kno wn 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 AN P gene, which is known to contain regulatory elements which modify gen e transcription. No gross alterations in the ANP gene or differences i n allelic frequencies at the RFLP sites within the gene were observed. PCR-SSCP analysis of the 5' proximal promoter region of the gene reve aled mutations in 10 patients in the -595 to -384bp region (19% of pat ients). Mutations in the 5' proximal promoter region of the ANP gene m ay contribute to altered ANP transcription in at least a proportion of patients with familial glaucoma. (C) 1996 Academic Press, Inc.