title: Genotype-phenotype variability in human CYP3A locus in Nepalese people residing in Bangladesh.
abstract: OBJECTIVE
  The study has been designed to phenotype 200 Nepalese people residing in Bangladesh by measuring urinary ratio of 6β-hydroxycortisol/cortisol (metabolic ratio) and to genotype all the subjects for the presence of CYP3A4*1B, *2, *4, *5, *6, *10, *18, CYP3A5*3, and *6 alleles.
  
  
  METHODS
  Cortisol and 6β-hydroxycortisol were extracted and quantified from morning spot urine samples (n = 200) by HPLC. Genotyping was carried out using the extracted genomic DNA by amplification of target alleles by PCR. Amplified DNA was digested by appropriate restriction enzymes followed by gel electrophoresis and sequencing to identify the targeted alleles.
  
  
  RESULTS
  A wide ratio of 6β-hydroxycortisol/cortisol was found (0.71 - 10.61) with an average of 4.41. No sample (n = 200) was found positive for CYP3A4*1B, *2, *4, *5, *6, *10, *18, and CYP3A5*6 alleles. CYP3A5*1/*1, *1/*3, and *3/*3 genotype frequency were found to be 20%, 20%, and 60%, respectively. A significantly higher mean metabolic ratio (MR) ± SD (MR = 6.28 ± 3.43) was found for CYP3A5*1/*1 compared to both CYP3A5*1/*3 (MR = 3.68 ± 1.37) and CYP3A5*3/*3 (MR = 3.58 ± 1.95).
  
  
  CONCLUSIONS
  This study demonstrates the absence of common CYP3A4 variant alleles in Nepalese people residing in Bangladesh whereas Nepalese people carrying the CYP3A5*1/*1 genotype appear to show a significantly higher 6β-hydroxycortisol/cortisol ratios compared to those with CYP3A5*3/*3 genotype.
authors: Department of Clinical Pharmacy and Pharmacology, University of Dhaka, Dhaka, Bangladesh.
authors: Rajib
authors: R
authors: Hassan
authors: Syeda Sadia
authors: SS
authors: Ameen
authors: Abdullah
authors: A
authors: Al Maruf
authors: Ananna
authors: A
authors: Nandini
authors: Humayra
authors: H
authors: Tabin
authors: Maizbha Uddin
authors: MU
authors: Ahmed
authors: Mohammad Safiqul
authors: MS
authors: Islam
authors: Muhammad Shahdaat
authors: MS
authors: Bin Sayeed
authors: Abul
authors: A
authors: Hasnat
mesh_terms: D000328:Adult; D000483:Alleles; D001459:Bangladesh / Q000453:epidemiology; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D008297:Male; D009390:Nepal / Q000208:ethnology; D010641:Phenotype
chemical_list: C001380:6 beta-hydroxycortisol; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006854:Hydrocortisone