Polymorphism of the β-2 adrenoceptor and IOP lowering potency of topical timolol in healthy subjects

Purpose: β-2 Adrenoceptor antagonists such as timolol have been used in the treatment of glaucoma for more than 30 years. Several functionally important polymorphisms for the β-2 receptor have been described. In the present study we hypothesized that a relation between the intraocular pressure (IOP) lowering effect of timolol and β-2 adrenoceptor polymorphisms may exist. Methods: A total of 270 healthy nonsmoking subjects were screened and individuals homozygous for the wild β-2 Adrenoceptor (Arg16/Gln27) and two polymorphisms (Gly16/Gln27 or Gly16/Glu27) were included. In these subjects the IOP lowering effect of timolol was compared. Results: Twenty-four subjects were included in the group Arg16/Gln27, 18 subjects in the group Gly16/Gln27, and 47 subjects in the group Gly16/Glu27. The ocular hypotensive effect of timolol was between 40 and 45% in all groups, but not significantly different between the three study groups (p=0.979). Conclusions: The present study indicates that the β-2 adrenoceptor polymorphism does not influence the ocular hypotensive effects of topical β adrenoceptor antagonists. Accordingly, other factors appear to be responsible for the intersubject variability seen with timolol in glaucoma subjects.