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Lookup NU author(s): Professor Ann DalyORCiD,
Dr Abul Hasnat
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Background: To investigate whether interindividual variation in CYP3A levels can partly be explained by genetic polymorphisms, this study was designed to phenotype 200 healthy Bangladeshi subjects by measuring urinary ratio of 6 beta-hydroxy-cortisol/cortisol and to genotype all the subjects for the presence of CYP3A4*1B, *2, *4, *5, *6, *10 and *18 and CYP3A5*3 alleles. Methods: For phenotyping, cortisol and 6 beta-hydroxy-cortisol were extracted and quantified by HPLC from morning spot urine samples (n = 200). Genotyping was done using the extracted genomic DNA from all the subjects followed by amplification of target alleles by PCR. Amplified DNA was digested by restriction enzymes (MbolI, XcmI, BsmAI, ClaI, HinfI, HpyCH4III, HpaII and RsaI) followed by gel electrophoresis and sequencing to identify the targeted alleles. Results: The ratio of 6 beta-hydroxy-cortisol/cortisol ranged from 0.01 to 31.98 with an average of 3.91. No sample (n = 200) was positive for CYP3A4*2, *4, *5, *6, *10 and *18 alleles. Two samples heterozygous for CYP3A4*1B (1.0%) and twenty six samples with the genotype CYP3A5*1/*1 (13.0%) were found to have relatively high 6 beta-hydroxy-cortisol/cortisol ratios. Conclusion: CYP3A4 variant alleles are present at a low frequency in the Bangladeshi population whereas 50% of the Bangladeshi population carrying a CYP3A5*3/*3 genotype appear to show lower 6 beta-hydroxy-cortisol/cortisol ratios compared with those with a CYP3A5*1/*1 genotype. (C) 2010 Elsevier B.V. All rights reserved.
Author(s): Al Maruf A, Ahmed MU, Yasmin H, Ullah MA, Azad MAK, Daly AK, Hasnat A
Publication type: Article
Publication status: Published
Journal: Clinica Chimica Acta
Print publication date: 27/11/2010
ISSN (print): 0009-8981
ISSN (electronic): 1873-3492
Publisher: Elsevier BV
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