Associations of rs4244285 in the CYP2C19 gene with multifactorial diseases

Abstract

Xenobiotic metabolism system in the current populations is involved in the biotransformation of a wide range of endogenous substrates and various xenobiotics, which can contribute to developing the diseases of various organ systems, and, in some cases, comorbid conditions where increased biotransformation system activity is observed. In this regard, it is of great interest to study the involvement of polymorphism in xenobiotic metabolism genes in the development of both isolated pathology and various comorbid conditions.Aim. The goal of study was to investigate the involvement of rs4244285 in the CYP2C19 gene in the development of isolated pathology and comorbidities.Material and Methods. The frequencies of alleles and genotypes were studied in groups of patients with comorbid conditions including groups of coronary artery disease (CAD) with hypertension (HTN) (CAD_HTN, n = 133) and bronchial asthma (BA) with HTN (BA_HTN, n = 178), in group of isolated BA (n = 135), and in the population sample of the city of Tomsk (n = 377). Association analysis covered three initial groups of patients (CAD, BA, and BA_HTN) and subgroups assigned based on the presence of absence of HTN diagnosis taking into account comorbid conditions both in patient samples and in population control.Results and Discussion. The study demonstrated the predisposing eff ect of GA genotype on the development of comorbid BA and HTN (OR = 1.94, p = 0.038) and comorbid CAD and HTN (OR = 2.26, p = 0.009) compared to isolated BA. The AA genotype was observed 3.98 times less often in HTN patients than in normotensive individuals. However, the diff erences did not reach the level of statistical signifi cance due to the low occurrence of this genotype.Conclusion. The obtained results may be explained by the involvement of CYP2C19-metabolites of arachidonic acid in the regulation of vascular tone, which requires further study.