CYP3A phenotypes and genotypes in North Indians.
OBJECTIVE
To phenotype 200 healthy North Indians for cytochrome P450 3A (CYP3A) activity by measuring urinary ratio of 6beta-OH-cortisol/cortisol (6beta-OH-CS/CS) and to genotype the subjects demonstrating low and high CYP3A activity for the presence of CYP3A4*1B, *2, *4, *5, *6 and *10 alleles.


METHODS
Morning spot urine samples were collected from 200 healthy North Indians. CS and 6beta-OH-CS were extracted and quantified by HPLC. Genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP).


RESULTS
Urinary 6beta-OH-CS/CS ratio demonstrated a mean of 52.0 +/- 46 (1.1-290). North Indians demonstrated unimodal distribution with respect to urinary 6beta-OH-CS/CS ratio. On the basis of phenotypes, the subjects were divided into three groups demonstrating low (n = 50), intermediate (n = 100) and high (n = 50) CYP3A activity. These groups demonstrated 6beta-OH-CS/CS ratio of 13.4 +/- 5.2 (1.1-21.0), 40 +/- 11.9 (21.2-63.2) and 114 +/- 51.0 (66-290), respectively. One hundred subjects, 50 in the low and 50 in the high activity group, were genotyped for CYP3A4*1B, *2, *4, *5, *6 and *10. Only 2 heterozygotes with genotype CYP3A4*1/*1B were found in the high CYP3A activity group. CYP3A4*2, *4, *5, *6 and *10 were not found in the subjects studied.


CONCLUSIONS
This is the first investigation establishing CYP3A phenotypes and demonstrating the absence of common CYP3A4 genotypes in North Indians.
Rais
Naushad
N
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, UT-160 012, India.
Chawla
Yogesh K
YK
Kohli
Krishan K
KK
D000328:Adult; D000483:Alleles; D001483:Base Sequence; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007194:India; D008297:Male; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic
D017931:DNA Primers; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; D006854:Hydrocortisone