Publisher： Spandidos Publications
ISSN： 1792-0981
Source： Experimental and Therapeutic Medicine, Vol.5, Iss.2, 2013-01, pp. : 527-532
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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 6βhydroxylation 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 6βhydroxycortisol/cortisol (6βOHCS/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 highperformance liquid chromatography. Furthermore, genotyping for CYP3A5*3 and CYP3A5*6 was performed by PCRRFLP. 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 6βOH-CS levels and log 6βOHCS/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, 0.220.36) and 0.71 (95% CI, 0.640.78), 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 6βOHCS/CS ratios were 110, 76 and 69 in wildtype 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 6βOHCS/CS ratio reflecting the CYP3A phenotypes.
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