CYP3A phenotypes and genotypes in North Indians
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To phenotype 200 healthy North Indians for cytochrome P450 3A (CYP3A) activity by measuring urinary ratio of 6β-OH-cortisol/cortisol (6β-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.
Morning spot urine samples were collected from 200 healthy North Indians. CS and 6β-OH-CS were extracted and quantified by HPLC. Genotyping was performed by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP).
Urinary 6β-OH-CS/CS ratio demonstrated a mean of 52.0 ± 46 (1.1–290). North Indians demonstrated unimodal distribution with respect to urinary 6β-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 6β-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.
This is the first investigation establishing CYP3A phenotypes and demonstrating the absence of common CYP3A4 genotypes in North Indians.
KeywordsCytochrome P450 3A Genetic polymorphism Pharmacogenetics Pharmacogenomics
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