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[Polymorphisms of genesencoding enzymes of the xenobiotic detoxification system and the risk of infectious

N V Mal'tseva, T A Laputenko, Ya A Gorbatovsky

    Klinicheskaia Meditsina
    |October 6, 2018
    PubMed

    Insights

    Infectious endocarditis (IE) risk is linked to specific genetic variations in drug-metabolizing enzymes. Certain gene variants significantly increase IE risk, especially in high-risk individuals.

    Area of Science:

    • Pharmacogenomics
    • Infectious Diseases
    • Cardiovascular Medicine

    Background:

    • Infectious endocarditis (IE) is often linked to medications metabolized by the xenobiotic detoxification system (XDS).
    • Understanding genetic predispositions within the XDS may clarify IE pathogenesis.

    Purpose of the Study:

    • To investigate the association between IE and single nucleotide polymorphisms (SNPs) in genes encoding XDS enzymes.
    • To identify specific XDS gene variants that may increase susceptibility to IE.

    Main Methods:

    • Genotyping of 46 IE patients and 114 controls for CYP1A1 I462V and GSTP1 I105V/A114V polymorphisms using allele-specific PCR.
    • Statistical analysis to determine the association between genotypes and IE.

    Main Results:

    • A significant association was found between IE and the CYP1A1 I462V and GSTP1 I105V polymorphisms.
    • No association was observed between IE and the GSTP1 A114V polymorphism.
    • A combination of homozygous CYP1A1 I462I and heterozygous GSTP1 I105V/ genotypes increased IE risk ninefold in individuals with specific risk factors (IV drug use, heart conditions, valve prostheses).

    Conclusions:

    • Specific XDS gene polymorphisms, particularly CYP1A1 I462V and GSTP1 I105V, are associated with infectious endocarditis.
    • Further research is warranted to explore the role of the XDS in the pathogenesis of IE and other infectious diseases.

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