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

Rais , Naushad and Hussain , Arif and Chawla, Yogesh Kumar and Kohli, Krishan k. (2012) Association between urinary 6β-hydroxycortisol/cortisol ratio and CYP3A5 genotypes in a normotensive population. Experimental and Therapeutic Medicine, 5 (2). pp. 527-532. ISSN 1792-0981

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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.

Item Type: Article
Subjects: Engineering > Dubai Campus > School of Life Sciences
Depositing User: Admin MU Dubai
Date Deposited: 18 Mar 2015 12:08
Last Modified: 22 Mar 2015 05:52
URI: http://eprints.manipal.edu/id/eprint/142158

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