Влияние индивидуальных генетических особенностей организма на успешность применения антибактериальных препаратов

Abstract

To date, numerous studies have reported significant associations of adverse drug reactions with genetic factors. In particular, the connection between drug-induced liver injury and carriage of certain MNS haplotypes when using amoxicillin and flucloxacillin has been demonstrated. The influence of polymorphisms of the PTPN22, ERAP2, PXR, ST6GAL1 genes was also observed. The pharmacokinetics of cephalosporins is affected by polymorphisms of drug transporter genes such as SLCO1A2, SLC22A8, ABCC2, ABCG2, ABCB1, which, however, requires further clarification. The pharmacokinetics of macrolides, according to some reports, may be related to the CYP3A4, SLCO1B1, ABCC2, and ABCB1 genes. The association of mutations in the mitochondrial DNA 12S rRNA genes in the development of non-syndromic and aminoglycoside-induced hearing loss has been well studied. The most important are the substitutions m.1095C>T, m.1494C>T and m.1555A>G. Risk factors for the development of neurological adverse reactions during the use of fluoroquinolones may be the carriage of alleles of blood-brain barrier transporters: ABCB1, ABCG2, SLCO1A2. Cutaneous adverse reactions with vancomycin may be associated with carrying MNS haplotypes, and urinary tract adverse reactions with the rs2789047 polymorphism. Daptomycin rarely contributes to the development of myopathy, which is presumably influenced by both renal functional status and the ABCB1 gene polymorphism. Key words: pharmacogenetics, genetic polymorphism, single nucleotide polymorphisms, antibiotics, adverse reactions