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Article

Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population

  • Authors:
    • Naushad Rais
    • Arif Hussain
    • Yogesh Kumar Chawla
    • Krishan K. Kohli
  • View Affiliations / Copyright

    Affiliations: Department of Biotechnology, Manipal University, Dubai, United Arab Emirates, Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India, Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India
  • Pages: 527-532
    |
    Published online on: November 29, 2012
       https://doi.org/10.3892/etm.2012.842
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Abstract

Genetic polymorphism of genes involved in renal salt handling and arterial vessel tone is considered to be one of the causes of hypertension. Numerous reports suggest that cytochrome P4503A5 (CYP3A5) catalyzes 6β‑hydroxylation of endogenous cortisol (CS), which is associated with sodium and water retention in the kidney and involved in the regulation of blood pressure. The purpose of the present study was to study the associations of single nucleotide polymorphisms in the CYP3A5 gene with the urinary 6β‑hydroxycortisol/cortisol (6β‑OH‑CS/CS) ratio considered as quantitative phenotypes. CS measurements of three hundred (n=300) healthy, normotensive North Indian individuals was performed on morning spot urine samples by high‑performance liquid chromatography. Furthermore, genotyping for CYP3A5*3 and CYP3A5*6 was performed by PCR‑RFLP. The results indicated a unimodal distribution of CYP3A phenotypes in the North Indian population. In further analysis, all the phenotypes were distributed into three groups, demonstrating low (n=75), intermediate (n=150) and high CYP3A activity (n=75) based on CS and 6β‑OH-CS levels and log 6β‑OH‑CS/CS ratios. The subjects in the low and high activity groups were genotyped for the CYP3A5*3 and *6 alleles. The present study demonstrated that the allele frequencies of CYP3A5*1 and *3 were 0.29 (95% CI, 0.22‑0.36) and 0.71 (95% CI, 0.64‑0.78), respectively. Notably, the frequency of normal homozygotes (CYP3A5*1/*1) was significantly higher in the high activity than the low activity group (11% vs. 5%). Similarly, the frequency of mutant homozygotes (CYP3A5*3/*3) was significantly higher in the low activity group than the high activity group (57% vs. 44%). The allele frequency of CYP3A5*3 was significantly higher in the low activity group (0.76) than the high activity group (0.67). The mean 6β‑OH‑CS/CS ratios were 110, 76 and 69 in wild‑type homozygotes (n=12), heterozygotes (n=62) and mutant homozygotes (n=76), respectively. The difference between the normal and mutant homozygotes was statistically significant (P<0.05). The CYP3A5*6 allele was absent from all the subjects genotyped. This is the first study to report the genetic polymorphism of CYP3A5 in a North Indian population and its association with urinary 6β‑OH‑CS/CS ratio reflecting the CYP3A phenotypes.
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Copy and paste a formatted citation
Spandidos Publications style
Rais N, Hussain A, Chawla YK and Kohli KK: Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population. Exp Ther Med 5: 527-532, 2013.
APA
Rais, N., Hussain, A., Chawla, Y.K., & Kohli, K.K. (2013). Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population. Experimental and Therapeutic Medicine, 5, 527-532. https://doi.org/10.3892/etm.2012.842
MLA
Rais, N., Hussain, A., Chawla, Y. K., Kohli, K. K."Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population". Experimental and Therapeutic Medicine 5.2 (2013): 527-532.
Chicago
Rais, N., Hussain, A., Chawla, Y. K., Kohli, K. K."Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population". Experimental and Therapeutic Medicine 5, no. 2 (2013): 527-532. https://doi.org/10.3892/etm.2012.842
Copy and paste a formatted citation
x
Spandidos Publications style
Rais N, Hussain A, Chawla YK and Kohli KK: Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population. Exp Ther Med 5: 527-532, 2013.
APA
Rais, N., Hussain, A., Chawla, Y.K., & Kohli, K.K. (2013). Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population. Experimental and Therapeutic Medicine, 5, 527-532. https://doi.org/10.3892/etm.2012.842
MLA
Rais, N., Hussain, A., Chawla, Y. K., Kohli, K. K."Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population". Experimental and Therapeutic Medicine 5.2 (2013): 527-532.
Chicago
Rais, N., Hussain, A., Chawla, Y. K., Kohli, K. K."Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population". Experimental and Therapeutic Medicine 5, no. 2 (2013): 527-532. https://doi.org/10.3892/etm.2012.842
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