Association between genetic polymorphisms of adrenergic receptor and diurnal intraocular pressure in Japanese normal-tension glaucoma

Purpose: To evaluate the relationship between genetic polymorphisms of the adrenergic receptor (ADR) and diurnal intraocular pressure (IOP) in Japanese normal-tension glaucoma (NTG) patients.

Design: Prospective, comparative case series.

Participants: Ninety-two untreated NTG patients.

Methods: The IOP of both eyes was measured at 3-hour intervals from 0600 to 2400 hours over 2 consecutive days. We used IOP data from the eye with the greater visual field defect for statistical analysis. The mean IOP over 2 days was used for each time point. Genetic polymorphisms in α1A-, α2A-, α2B-, α2C-, β1-, β2-, and β3-ADR were determined mainly by direct DNA sequencing. The relationship between IOP and genetic polymorphisms was analyzed.

Main outcome measures: The IOP and genotypes of genetic polymorphisms.

Results: Diurnal mean IOP of the subjects was 14.8 ± 2.1 mmHg (mean value ± standard deviation). For Del 301-303 in α2B-ADR, insertion/insertion (I/I) had a significantly higher diurnal mean IOP (P = 0.017), peak IOP (P = 0.038), and trough IOP (P = 0.046) than deletion (D) carriers. For Del 322-325 in α2C-ADR, I/I had a significantly lower diurnal mean IOP (P = 0.037) and peak IOP (P = 0.029) than D carriers. For S49G (A/G) in β1-ADR, A/A had a significantly higher diurnal mean IOP (P = 0.023), peak IOP (P = 0.019), and trough IOP (P = 0.014) than G carriers. For these 3 polymorphisms, repeated measures analysis of variance showed that the major homozygotes and minor carriers had parallel diurnal IOP curves, but significantly different diurnal IOP levels.

Conclusions: Polymorphisms of the ADR gene may alter the untreated IOP level of patients with NTG.