CYPs Genotyping, Essential Hypertension and Frequencies of Mutant Alleles in an Uzbek Population
Background and Objectives: Each patient has a combination of the genes bound to cardiovascular illnesses. The aim of our study was to determine the features of the distribution of genes associated with hypertension. In this paper we have described the 4 polymorphic loci distinctive susceptibility to hypertension. There are 4 polymorphisms of genes in nuclear DNA (CYP2C19 *2 CYP3A5, CYP2C9-3 and CYP2C9-2).
Materials and Methods: The study included 109 Uzbek men (mean age 48 ± 11 years) with untreated EH of stage 1-2 and 82 normotensive males.
Results: Distribution of allele frequency of, CYP2C19 *2 CYP3A5, CYP2C9-3 and CYP2C9-2 genes was similar with Saudi Arabian, Afro-American, Spain and European American population respectively. Registration of the genotyping results has identified an association CYPs gene (CYP2C9-2; CYP3A5) with the risk of EH. The CYP2C9-*2 allele showed a higher association with hypertension in comparison to the *1 allele (OR 3.89, 95% CI 0.48-10.20). In the analysis of cytochrome P450 in patients with EH, we have identified two common point of nucleotide substitutions (*2,*3). We have determined that monogenic Western and hybrid Eastern population of Uzbekistan are often carriers of damaging *2/*2 -genotype of CYP2C9-2 and *1/*3-*3/*3 genotype of CYP3A5 gene. Distribution of allele frequency was the most closely with American.
Conclusion: In the present study, we investigated the association between genotype variants of the CYPs genes and EH in Uzbek population. We found that the *2/*2 polymorphism of the CYP2C9-2 gene was associated with EH in Uzbek hypertensive patients. A separate analysis of case-control studies (CYP2C9-3: CYP2C19*2 genes) from Uzbekistan showed no significant differences in allele and genotype frequencies between hypertensive patients and normotensive control subjects. According to our opinion, the results are only preliminary and further large case-control studies in our and other Central Asia populations are needed to confirm this association.