Intergenic interactions and the contribution of polymorphic gene loci of enzymes involved in free radical processes in pathozoospermia

Background. About 40-50% of male infertility cases are due to pathozoospermia. Assessment of gene - gene interactions associated with pathospermia is an important task. Aim: to analyze the intergenic interactions of PON1 (Q192R), SOD1 (G7958A), CAT (C262T), NOS3 (C786T) and hOGG1 (Ser326Cys) polymorphisms in pathozoospermia. Methods. The study included 130 residents of the Rostov region. The comparison group consisted of 80 men with pathospermia, aged 23 to 48 years. The control group was formed from 50 sperm donors, collaborated with «The center of human reproduction and IVF». Determination of SNP was carried out using allele-specific polymerase chain reaction. Differences in the distribution of allelic variants of genes in the examined groups were assessed using the χ2 criterion. The risk of developing pathozoospermia was judged by the odds ratio. Modeling of intergenic interactions of polymorphic loci of PON1, SOD1, NOS3, CAT, hOGG1 genes was performed using the Multifactor Dimensionality Reduction software. Results. As a result of the study, the frequencies of genotypes and alleles were determined for polymorphic variants of the genes of enzymes involved in free radical processes in men with pathozoospermia. A significant model of intergenic interactions of polymorphic loci of the studied genes was revealed, affecting the risk of developing pathozoospermia, characterized by a cross-validation coefficient of 10/10 and a prediction accuracy of 78% (χ2 = 36.74 (p <0.0001), OR = 12.27, 95% CI 5.09 - 29.55). Conclusions. As a result of the analysis of intergenic interactions of polymorphic variants of the PON1, SOD1, NOS3, CAT, hOGG1 genes in the development of pathozoospermia using the Multifactor Dimensionality Reduction method, statistically significant associations were found that lead to an increase in the risk of developing this pathology.

male infertility, pathozoospermia, polymorphism, oxidative stress, MDR

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