The association between CYP3A5 genotype and antihypertensive response

Abstract

In young African Americans (AA) the CYP3A5 genotype has been suggested to be associated with a higher blood pressure. Using real time PCR, we tested for the CYP3A5*3 allele in 412 subjects (58% Caucasians, 52% hypertensives, 77% men) and classified them as *1/*1, *1/*3, or *3/*3. Most of the hypertensive subjects (as defined by JNC 7) were on one or more antihypertensive drugs (calcium channel blockers, diuretics, ACE inhibitors, angiotensin receptor blockers, direct vasodilators, β-blockers, α-1-blockers, and clonidine). A regression analysis showed no association between BMI and the *1 allele (r2 =0.021, p=0.06) in AAs. The *1 allele was found to be more frequent in hypertensive African Americans (90% vs 81%, p=0.08 using Fisher's Exact Test). We also used the Mantel-Haenszel Chi-Square test to check if the CYP3A5 genotype is associated with ease of control of hypertension or if it is correlated with the number of medications. When we compared the group composed of normotensive and adequately controlled hypertensive AAs on one to two antihypertensive drugs versus those on three or more antihypertensive medications with poor BP control, we found that the frequency of the *1 allele is significantly greater with the latter group (64% for *1/*1, 36% for *1/*3 and none for *3/*3, p=0.05). All of the above tests were not significant for the Caucasians. There was a trend for the CYP3A5*1 allele to be associated with hypertension and its treatment with multidrug regimen in AAs. Clinical Pharmacology & Therapeutics (2004) 75, P62–P62; doi: 10.1016/j.clpt.2003.11.234