Genotypes and phenotypes of CYP3A in Bangladeshi population.
BACKGROUND
To investigate whether interindividual variation in CYP3A levels can partly be explained by genetic polymorphisms, this study was designed to phenotype 200 healthy Bangladeshi subjects by measuring urinary ratio of 6β-hydroxy-cortisol/cortisol and to genotype all the subjects for the presence of CYP3A4*1B, *2, *4, *5, *6, *10 and *18 and CYP3A5*3 alleles.


METHODS
For phenotyping, cortisol and 6β-hydroxy-cortisol were extracted and quantified by HPLC from morning spot urine samples (n=200). Genotyping was done using the extracted genomic DNA from all the subjects followed by amplification of target alleles by PCR. Amplified DNA was digested by restriction enzymes (MboII, XcmI, BsmAI, ClaI, HinfI, HpyCH4III, HpaII and RsaI) followed by gel electrophoresis and sequencing to identify the targeted alleles.


RESULTS
The ratio of 6β-hydroxy-cortisol/cortisol ranged from 0.01 to 31.98 with an average of 3.91. No sample (n=200) was positive for CYP3A4*2, *4, *5, *6, *10 and *18 alleles. Two samples heterozygous for CYP3A4*1B (1.0%) and twenty six samples with the genotype CYP3A5*1/*1 (13.0%) were found to have relatively high 6β-hydroxy-cortisol/cortisol ratios.


CONCLUSIONS
CYP3A4 variant alleles are present at a low frequency in the Bangladeshi population whereas 50% of the Bangladeshi population carrying a CYP3A5*3/*3 genotype appear to show lower 6β-hydroxy-cortisol/cortisol ratios compared with those with a CYP3A5*1/*1 genotype.
Department of Clinical Pharmacy & Pharmacology, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh.
Abdullah
A
Al Maruf
Maizbha Uddin
MU
Ahmed
Hasina
H
Yasmin
Md Ashik
MA
Ullah
M A K
MA
Azad
Ann K
AK
Daly
Abul
A
Hasnat
D000293:Adolescent; D000328:Adult; D001459:Bangladesh; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D016133:Polymerase Chain Reaction; D055815:Young Adult
C001380:6 beta-hydroxycortisol; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D006854:Hydrocortisone