medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2021.11.36-44medgen-1997Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHМежгенные взаимодействия и вклад полиморфных локусов генов ферментов, принимающих участие в свободнорадикальных процессах при патозооспермииIntergenic interactions and the contribution of polymorphic gene loci of enzymes involved in free radical processes in pathozoospermiaСавикинаК. Г.SavikinaK. G.otuscops88@gmail.comМашкинаЕ. В.MashkinaE. V.noemail@neicon.ruАлександроваА. А.AleksandrovaA. A.noemail@neicon.ruШкуратТ. П.ShkuratT. P.noemail@neicon.ruЛомтеваС. В.LomtevaS. V.noemail@neicon.ruООО «Центр репродукции человека и ЭКО»РоссияLLC “Center for Human Reproduction and IVF”Russian FederationАкадемия биологии и биотехнологии им. Д.И. Ивановского ЮФУРоссияAcademy of Biology and Biotechnology Southern Federal UniversityRussian Federation20212801202220113644Copyright © Савикина К.Г., Машкина Е.В., Александрова А.А., Шкурат Т.П., Ломтева С.В., 20222022Савикина К.Г., Машкина Е.В., Александрова А.А., Шкурат Т.П., Ломтева С.В.Savikina K.G., Mashkina E.V., Aleksandrova A.A., Shkurat T.P., Lomteva S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medgen-journal.ru/jour/article/view/1997

Введение. Около 40-50% случаев мужского бесплодия обусловлено патозооспермией. Оценка ген-генных взаимодействий, ассоциированных с патоспермией является важной задачей. Цель: проведение анализа межгенных взаимодействий полиморфизмов генов PON1(Q192R), SOD1(G7958A), CAT(C262T), NOS3(C786T) и hOGG1(Ser326Cys) при патозооспермии. Методы. В исследование включены 130 жителей Ростовской области. Группу сравнения составили 80 мужчин с патоспермией в вoзрacтe от 23 до 48 лет. Контрольная группа была сформирована из 50 доноров спермы, сотрудничавших с ООО «Центр репродукции человека и ЭКО». Определение SNP было проведено методом аллель-специфичной полимеразной цепной реакции. Оценку различий в распределении аллельных вариантов генов в обследованных группах осуществляли по критерию χ2. О риске развития патозооспермии судили по отношению шансов. Для моделирования межгенных взаимодействий полиморфных локусов генов PON1, SOD1, NOS3, CAT, hOGG1 использовали программное обеспечение Multifactor Dimensionality Reduction. Результаты. В результате исследования определены частоты генотипов и аллелей по полиморфным вариантам генов ферментов, участвующих в свободнорадикальных процессах у мужчин с патозооспермией. Выявлена значимая модель межгенных взаимодействий полиморфных локусов исследуемых генов, влияющая на риск развития патозооспермии, характеризующаяся коэффициентом перекрестной проверки 10/10 и точностью предсказания 78% (χ2= 36,74(р<0,0001), OR=12,27, 95% CI 5,09 - 29,55). Заключение. В результате анализа межгенных взаимодействий полиморфных вариантов генов PON1, SOD1, NOS3, CAT, hOGG1 в развитии патозооспермии с использованием метода Multifactor Dimensionality Reduction были найдены статистически значимые ассоциации, приводящие к увеличению риска развития данной патологии.

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.

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The authors declare that there are no conflicts of interest present.