¹ International Medical Research and Development Corporation; New York, NY, USA.
² Arterial Hypertension Department, Republican Specialized Center of Cardiology; Tashkent, Republic of Uzbekistan.
*Corresponding author: Amayak G. Kevorkov, PhD Arterial Hypertension Department, Republican Specialized Center of Cardiology, 4, Osiyo str., 100052 Tashkent, Uzbekistan. Tel:998-97-4455279; E-mail: amayak.kevorkov@gmail.com
Cytochrome P450 microsomal enzymes, a superfamily of heme-containing proteins, catalyze the most important phase I of biotransformation reactions.CYP3A enzymes are the most abundantly expressed cytochrome P450 enzymes in liver and they are responsible for the metabolism of over 50% of drugs. The CYP3A5 contribution to drug metabolism vary from 6-99% of the total CYP3A activity in different populations. Therefore, CYP3A5 may be an important genetic contributor to interindividual and interracial differences in CYP3A-dependent drug clearance and response. The major determinant for this variation in expression is a single-nucleotide polymorphism in intron 3 at position 6986. Also, CYP3A enzymes metabolize cortisol into 6β-hydroxycortisol, a physiological regulator of sodium transport in renal epithelia, and renal CYP3A5-produced 6β-hydroxycortisol may play a key role in increasing sodium and water retention and blood pressure elevation.
Purpose: to present the results of investigation of the CYP3A5 A6986G SNP in Uzbek hypertensive men by polymerase chain reaction-restriction fragment length polymorphism-based analysis.
Material and methods: 80 unrelated Tashkent residing Uzbek men with arterial hypertension I-II grade in the mean age 44.97±9.50 were included into the study, after receiving the informed consent. Genomic DNA was extracted from the whole blood samples. After the PCR amplification the DNA fragment of 133bp was obtained. The PCR product was then digested with the RsaI restriction enzyme.
Results: 23 samples (28.75%) were found to be heterozygous for the CYP3A5*3 allele with the remainder (71.25%) being homozygous for this allele (χ2=28.90; p=0.000). Frequencies of the two alleles in the studied population were therefore 0.1438 for CYP3A5*1 and 0.8562 for CYP3A5*3 respectively (χ2=162.42; p=0.000). All genotype and allele frequencies were in Hardy-Weinberg equilibrium.
Conclusion: results of our study demonstrates significant prevalence of *3 allele and *3/*3 genotype of CYP3A5 in Uzbek hypertensive men.
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