Deficient nifedipine oxidation: a rare inherited trait associated with cystic fibrosis kindreds.
Previous studies have indicated that there is weak genetic linkage between the defective gene in cystic fibrosis (CFTR) and the gene encoding the nifedipine metabolizing enzyme P4503A4 which are both located on chromosome 7. To examine further this possible association, nifedipine metabolism was investigated in a group of 59 volunteers, and 17 adult cystic fibrosis patients and 37 of their relatives. In agreement with the majority of previous studies, the volunteer group showed a unimodal distribution of recoveries for the major metabolite M-II ranging from 33 to 78% excretion in 8 h. In the case of both the cystic fibrosis patients and their parents, the distribution of recoveries was shifted to the left with five out of 20 parents and three out of 11 unrelated cystic fibrosis patients showing recoveries below the range observed in the volunteer group. This poor metabolism appeared to be both reproducible and heritable and did not appear to be a consequence of mutations in the CFTR gene.
Daly
A K
AK
Department of Pharmacological Sciences, University of Newcastle upon Tyne, Medical School, UK.
Salh
B S
BS
Bilton
D
D
Allen
J
J
Knight
A D
AD
Webb
A K
AK
Braganza
J M
JM
Idle
J R
JR
D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009543:Nifedipine / Q000378:metabolism*; D010084:Oxidation-Reduction; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000378:metabolism; D010375:Pedigree; D010641:Phenotype; D011110:Polymorphism, Genetic
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D009543:Nifedipine