The role of genes of the first phase of xenobiotic metabolism on the cystic fibrosis severity and response during antibiotic treatment in cystic fibrosis

Associations of the first phase xenobiotic biotransformation system genes with the severity of cystic fibrosis (CF), adverse side effects and antibiotic resistance to intravenious antibiotic therapy in CF children were studied in the presented survey. The number of examined CF children amounted to 118, healthy sample of 70 individuals. All surveyed children reside in the European part of Russia. Study of 6 polymorphisms in 4 genes of the first phase biotransformation system of xenobiotics, CYP2C9, CYP2C19, CYP2D6, CYP3A4 was carried out by RFLP analysis. There were no significant differences in the frequency of alleles and genotypes of the studied polymorphisms between the groups of healthy and children with CF, excluding the higher allele frequency of CYP2D6*4 in the total group of MV patients (p = 0,023), as well as between groups of CF patients that have the resistant to antibiotic therapy microflora of the respiratory tract, and not having such, and in groups of patients receiving 3 or more course of intravenous therapy for a year and receiving antibiotic therapy at least 2 times during the year. There is a tendency to increase the frequencies of CYP2C9*3 allele and heterozygous CYP2C9*3/CYP2C9*1 genotype in the group of children receiving intravenous antibiotic therapy sporadically or not receiving at all compared to receiving intravenous antibiotic therapy for more than 3 times a year (p<0,1). Association of CYP3A4*1B allele and CYP3A4*1B/*1A genotype with the adverse side effects to antibacterial drugs was identified (p = 0.023 and p = 0,025). The carrier state of the heterozygous genotype CYP3A4*1B/*1A and the carrier state of the CYP3A4*1B/*1A(-392C/T) Ч CYP2D6*1/*1(1846G/G) combined genotype can be regarded as markers for increased risk of adverse response to intravenous antibiotic therapy in CF patients (OR = 8,50 (95%CI of 1.64-44,04) and OR = 35,00 (95%CI 3,29-372,14), respectively).

муковисцидоз, гены первой фазы системы биотрансформации, цитохромы P450, антибиотикорезистентность, нежелательные побочные реакции на антибиотикотерапию у детей с муковисцидозом, Cystic Fibrosis, genes of the first phase biotransformation of xenobiotics, cytochrome P450 system, antibiotic resistance, adverse response to antibiotic therapy in CF children

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