ADRB1 and ADBR2 Gene Polymorphisms and the Ocular Hypotensive Response to Topical Betaxolol in Healthy Mexican Subjects

Background: The beta adrenergic receptors (ADRB) are expressed in the ciliary body and trabecular meshwork, structures involved in aqueous humor production and outflow, respectively. ADRB are members of the adrenergic family of G-protein-coupled receptors. Topic beta blockers have a good local and systemic tolerance; they reduce the aqueous humor production and eye strain blocking the ADRB of the ciliary body and interfering with adenylate cyclase. However, the ocular hypotensive response is not the same in all patients and could be mediated by the polymorphisms of the ADRB genes. Materials and methods: Seventy-two healthy subjects were studied after treatment with topical betaxolol in both eyes. We analyzed ADRB1 and ADRB2 gene polymorphisms by PCR and automated DNA sequencing. Results: There was statistically significant difference between baseline intraocular pressure (IOP) and final IOP of both eyes (baseline IOP 16.2 +/- 1.2 - follow-up IOP 13.6 +/- 2.0 (mean difference-2.5 +/- 1.3, p < 0.001). Gly389 had a higher baseline IOP than Arg389 (17.0 +/- 1.2 mm Hg versus 16.0 +/- 1.2 mm Hg; p = 0.02), and conversely Arg389 had a greater magnitude of response than Gly389 to betaxolol therapy (-2.9 +/- 1.1 mm Hg versus -0.7 +/- 0.4 mm Hg; p < 0.001). Gln27 had a higher response than Glu27 (-2.7 +/- 1.3mmHg versus -1.9 +/- 1.0; p = 0.02). Conclusion: Arg389 polymorphism of the ADRB1 gene and Gln27 polymorphism of the ADRB2 gene were associated with the hypotensive response to topic betaxolol in healthy Mexican volunteers.