RESUMO
OBJECTIVES: The study has been designed to phenotype 200 Nepalese people residing in Bangladesh by measuring urinary ratio of 6ß-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 6ß-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 6ß-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). CONCLUSION: 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 6ß-hydroxycortisol/cortisol ratios compared to those with CYP3A5*3/*3 genotype.
