Association of CYP3A5*3, *6, and *7 polymorphisms with hypertension

Purpose The CYP3A5 *3, *6, and *7 alleles have a greatly reduced capacity to produce functional CYP3A5 enzyme relative to the *1 allele. Polymorphic renal CYP3A5 expression may regulate blood pressure (BP) and risk of hypertension (HTN). A previous study of 25 young healthy African‐Americans (AA) showed an association between C YP3A5 genotype and BP. Methods A total of 564 AAs (n=266) and Caucasians (n=298) normotensives (NT) with no known family history of HTN and hypertensives (HT) with a family history of HTN were genotyped for CYP3A5 *3 (and *6 and *7 in AAs only) using pyrosequencing technology. CYP3A5 haplotypes for AAs were determined by computational methods. Functional allele status was determined based on *3 genotype for Caucasians (ie: *1,*3=1 functional allele) and *3, *6 and *7 diplotype for AAs (ie: *1, *1, *1/,*1, *6, *1=1 functional allele). Results There were no differences in functional allele/haplotype frequencies between HT (0.16) and NT Caucasians (0.11); p=0.21, or HT (0.60) and NT AAs (0.56); p=0.52. There were also no differences in BP (Mean ± SD) by number of functional alleles among NT AAs or Caucasians ( Table). Conclusion There was no association between hypertension or BP and CYP3A5 expressor (*1) versus nonexpressor (*3, *6, *7) alleles in AAs or Caucasians. Clinical Pharmacology & Therapeutics (2004) 75 , P13–P13; doi: 10.1016/j.clpt.2003.11.050Number of functional Alleles 0 1 2NT CaucasiansSBP 118.6 ± 11.52 117.1 ± 12.13 125.0 ± 18.38 DBP 75.6 ± 8.85 73.6 ± 6.19 77.0 ± 4.24 NT AAs 120.5 ± 8.62 116.5 ± 8.69 118.4 ± 19.80 SBP 77.3 ± 4.78 75.9 ± 7.24 76.9 ± 5.48 DBP