This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in this journal  Topic Collections  • Glaucoma  • Ophthalmological Disorders, Other  • Drug Therapy  • Drug Therapy, Other  • Genetics  • Genetics, Other  • Alert me on articles by topic  Social Bookmarking   What's this?

Catherine A. McCarty, PhD, MPH; James K. Burmester, PhD; Bickol N. Mukesh, PhD; Richard B. Patchett, MD; Russell A. Wilke, MD, PhD

Arch Ophthalmol. 2008;126(7):959-963.

Objectives  To determine whether candidate pharmacodynamic (β-adrenergic receptor) and pharmacokinetic (cytochrome P450 2D6) gene polymorphisms are associated with the intraocular pressure (IOP) response to topical β-blockers.

Methods  Medical records of 18 773 adults in the Personalized Medicine Research Project were searched to extract all IOP measurements for subjects who had been prescribed a topical β-blocker. Five single-nucleotide polymorphisms in the β₁-, β₂-, and β₃-adrenergic receptor genes and 6 polymorphisms in the CYP2D6 gene were genotyped.

Results  A total of 58.1% of the subjects were female; the mean age was 63.8 years. Topical β-blockers were prescribed for 343 eyes of 215 subjects. An IOP reduction of 20% or more in 1 or both eyes was observed in 61.0% of subjects. Men were significantly more likely than women to have an IOP decrease of 20% or more (69.3% vs 54.9%, respectively; ² = 4.48; P = .04). After adjusting for sex, family history of glaucoma, and use of systemic β-blockers, subjects with the CC genotype at coding single-nucleotide polymorphism rs1042714 in the ADRB2 gene were significantly more likely to experience an IOP decrease of 20% or more (odds ratio, 2.00; 95% confidence interval, 1.00-4.02).

Conclusion  We found that a coding single-nucleotide polymorphism in ADRB2 is associated with an increased likelihood of a clinically meaningful IOP response to topical β-blockers.

Clinical Relevance  Because topical β-blockers are the least expensive class of agents used to lower IOP, genotype-based drug prescribing could save health care dollars.

Author Affiliations: Center for Human Genetics (Drs McCarty, Burmester, and Wilke) and Biomedical Informatics Research Center (Dr Mukesh), Marshfield Clinic Research Foundation, and Department of Ophthalmology, Marshfield Clinic (Dr Patchett), Marshfield, Wisconsin; and Department of Medicine and Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee (Dr Wilke).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Methodologic Aspects of Glaucoma Phamacogenomic Studies
Christopher T. Leffler
Arch Ophthalmol. 2009;127(5):706.
EXTRACT | FULL TEXT  

Methodologic Aspects of Glaucoma Phamacogenomic Studies—Reply
Catherine A. McCarty, James K. Burmester, Bickol N. Mukesh, Richard B. Patchett, and Russell A. Wilke
Arch Ophthalmol. 2009;127(5):706-707.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Methodologic Aspects of Glaucoma Phamacogenomic Studies
Leffler
Arch Ophthalmol 2009;127:706-706.
FULL TEXT