CYP3A phenotypes and genotypes in North Indians

• Published in: European journal of clinical pharmacology 2006-06, Vol.62 (6), p.417-422
• Main Authors: Rais, Naushad, Chawla, Yogesh K, Kohli, Krishan K
• Format: Article
• Language: English
• Subjects: Adult; Alleles; Base Sequence; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System - genetics; DNA Primers - genetics; Female; Gene Frequency; Genotype; Humans; Hydrocortisone - analogs & derivatives; Hydrocortisone - urine; India; Male; Pharmacogenetics; Phenotype; Polymorphism, Genetic
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-006-0105-3

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. 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). 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. This is the first investigation establishing CYP3A phenotypes and demonstrating the absence of common CYP3A4 genotypes in North Indians.