Abstract
Abstract: :
Purpose: Polymorphisms in the beta–1 adrenergic receptor gene have been linked to clinical response of systemic beta–blockers for blood pressure control. We sought a possible correlation between genotype at codon 389 of this receptor with clinical response to topical 0.25% betaxolol (Betoptic–S, Alcon) in a small, pilot study of normal volunteers. Methods: Twenty–three normal volunteers were placed on topical betaxolol for 6 weeks. Clinical response was defined as lowering of the intraocular pressure (IOP), averaged between the two eyes, by at least 3 mmHg from baseline, at both the 3–week and 6–week follow–up examinations. The genotypes were determined by PCR with RFLP. Arginine (Arg) is wild–type and glycine (Gly) is non–wild–type at codon 389. Results:Of the 23 volunteers, there were 7 responders (30%) and 16 non–responders. For all volunteers, the mean change in IOP was –2.1 mmHg (SD 2.3, p<0.001). Eleven volunteers were Arg389 homozygotes; their mean change in IOP was –2.8 mmHg (SD 2.1). The remaining volunteers (11 Gly389 carriers, 1 Gly389 homozygote) had a smaller mean change in IOP of –1.5 mmHg (SD 2.3), but this trend was not statistically significant (p=0.17). Of all 23 volunteers, the allelic frequencies were 33/46 (72%) Arg and 13/46 (28%) Gly. Of the 7 responders, 4 (57%) were Arg389 homozygotes and 3 (43%) were Gly389 carriers. Of the 16 non–responders, 7 (44%) were Arg389 homozygotes, 8 (50%) were Gly389 carriers, and 1 was a Gly389 homozygote. Conclusions: In this small, pilot series, the response rate to ophthalmic betaxolol in normal volunteers was 30%, and the mean decrease in IOP was 2.1 mmHg. There was no statistically significant correlation between genotype at codon 389 and clinical response. Arg389 homozygotes tended to have a greater response to betaxolol than patients with other genotypes, but this trend was not statistically significant. Further studies are necessary to confirm these results, to explore a possible correlation regarding codon 49 of the receptor gene, and to explore possible correlations in patients with open–angle glaucoma or ocular hypertension.
Keywords: pharmacology • genetics • intraocular pressure