Polymorphism of the beta-2 adrenoceptor and IOP lowering potency of topical timolol in healthy subjects.
OBJECTIVE
Beta-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 beta-2 receptor have been described. In the present study we hypothesized that a relation between the intraocular pressure (IOP) lowering effect of timolol and beta-2 adrenoceptor polymorphisms may exist.


METHODS
A total of 270 healthy nonsmoking subjects were screened and individuals homozygous for the wild beta-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 beta-2 adrenoceptor polymorphism does not influence the ocular hypotensive effects of topical beta adrenoceptor antagonists. Accordingly, other factors appear to be responsible for the intersubject variability seen with timolol in glaucoma subjects.
Fuchsjager-Mayrl
Gabriele
G
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Markovic
Ognjen
O
Losert
Doris
D
Lucas
Trevor
T
Wachek
Volker
V
Muller
Markus
M
Schmetterer
Leopold
L
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D004252:DNA Mutational Analysis; D005838:Genotype; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage; D011110:Polymorphism, Genetic; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013999:Timolol / Q000008:administration & dosage*; D014065:Tonometry, Ocular
D000319:Adrenergic beta-Antagonists; D009883:Ophthalmic Solutions; D018343:Receptors, Adrenergic, beta-2; D013999:Timolol