Beta-1 adrenoceptor polymorphisms and response to betaxolol

Project Summary

Glaucoma is both more common and more severe among African-Americans. In most forms of this disease, high intraocular pressure causes progressive and irreversible damage. One of the most commonly used medications to lower eye pressure is betaxolol, an eye drop that blocks a protein inside the eye called the beta-1 adrenergic receptor. However, approximately 20% of all patients taking betaxolol do not respond adequately to the medication, and it is also known that African-Americans do not respond nearly as well to beta-blockers in comparison with other racial groups. In addition, some people have a mutation in a gene located on chromosome number 10 that leads to an abnormal and perhaps less active receptor protein. Interestingly, African-Americans are almost twice as likely to have this mutation than are Caucasians. Dr. Schwartz has hypothesized that a genetic mutation in the gene that makes the beta-1 adrenergic receptor protein may explain why betaxolol fails to lower eye pressure in certain patients. For this study, Dr. Schwartz will recruit 80 normal, healthy volunteers and treat them with betaxolol eye drops for 6 weeks. The primary aim is to determine which subjects are non-responders to betaxolol, and to determine if the genetic mutation plays a role in their lack of response. The second aim is to compare the response to betaxolol in African-Americans versus Caucasians and determine if there is a genetic-racial link to the lack of response. If the genetic mutation appears to be responsible for the lack of response to betaxolol, this will help explain why some patients do not respond to beta-blockers as a line of treatment.