Association of CYP2D6 Single-Nucleotide Polymorphism with Response to Ophthalmic Timolol in Primary Open-Angle Glaucoma-A Pilot Study

Objectives: We aimed to investigate whether CYP2D6 polymorphisms were associated with the intraocular pressure (IOP)-lowering effect and systemic complications (especially bradycardia) of ophthalmic timolol. Methods: One hundred twenty-three primary open-angle glaucoma subjects (123 eyes) were treated with 0.5% aqueous formulations of ophthalmic timolol. IOP and heart rate were measured before and after timolol administration. DNA was extracted from venous leukocytes of all the subjects. Two single-nucleotide polymorphisms (SNPs) of CYP2D6, for example, rs16947 (2850C>T, R296C) and rs1135840 (4180C>G, S486T), were detected by restriction fragment length polymorphism analysis. Results: Neither rs16947 (P=0.339) nor rs1135840 (P=0.903) genotype was statistically correlated with the IOP-lowering effect of timolol eye drops. The rs16947 genotype was significantly associated with occurrence of bradycardia in primary open-angle glaucoma patients (P=0.021). The patients with rs16947 CT (P=0.043) or TT (P=0.043) were more inclined to bradycardia than those with rs16947 CC, although there was no significant difference between CT and TT (P=0.177). The analysis of variance showed no significant difference in heart rate (P=0.559) among GG, GC, and CC groups. Conclusions: CYP2D6 SNP rs16947 may confer susceptibility to timolol-induced bradycardia. Patients with CC genotype were unlikely to suffer from timolol-induced bradycardia, whereas those with TT genotype were found to suffer from timolol-induced bradycardia.