Intraocular pressure response to topical beta-blockers associated with an ADRB2 single-nucleotide polymorphism.
OBJECTIVE
To determine whether candidate pharmacodynamic (beta-adrenergic receptor) and pharmacokinetic (cytochrome P450 2D6) gene polymorphisms are associated with the intraocular pressure (IOP) response to topical beta-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 beta-blocker. Five single-nucleotide polymorphisms in the beta(1)-, beta(2)-, and beta(3)-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 beta-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; chi(2) = 4.48; P = .04). After adjusting for sex, family history of glaucoma, and use of systemic beta-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).


CONCLUSIONS
We found that a coding single-nucleotide polymorphism in ADRB2 is associated with an increased likelihood of a clinically meaningful IOP response to topical beta-blockers. Clinical Relevance Because topical beta-blockers are the least expensive class of agents used to lower IOP, genotype-based drug prescribing could save health care dollars.
McCarty
Catherine A
CA
Center for Human Genetics, Marshfield Clinic Research Foundation, 1000 N Oak Ave, Marshfield, WI 54449, USA. mccarty.catherine@mcrf.mfldclin.edu
Burmester
James K
JK
Mukesh
Bickol N
BN
Patchett
Richard B
RB
Wilke
Russell A
RA
D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018797:Cell Cycle Proteins; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D005901:Glaucoma / Q000188:drug therapy / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D035582:Transcription Factor TFIIIA / Q000235:genetics; D000099179:Myocilin
D000319:Adrenergic beta-Antagonists; D018797:Cell Cycle Proteins; D019389:Cytochrome P-450 CYP2D6; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D026901:Membrane Transport Proteins; D018343:Receptors, Adrenergic, beta-2; D035582:Transcription Factor TFIIIA; D000099179:Myocilin; C409460:OPTN protein, human