medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2022.06.49-58medgen-2186Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHАссоциации между полиморфизмами гена XRCC1 и заболеваниями, вызванными атеросклерозом: мета-анализAssociations between XRCC1 gene polymorphisms and atherosclerosis-induced diseases: a meta-analysisТимофееваС. В.TimofeevaS. V.timofeeva.sophia@gmail.comШерчковаТ. А.SherchkovaT. A.noemail@neicon.ruШкуратТ. П.ShkuratT. P.noemail@neicon.ruЮжный Федеральный Университет, Академия биологии и биотехнологииРоссияSouthern Federal University, Academy of biology and biotechnologyRussian Federation2022091220222164958Copyright © Тимофеева С.В., Шерчкова Т.А., Шкурат Т.П., 20222022Тимофеева С.В., Шерчкова Т.А., Шкурат Т.П.Timofeeva S.V., Sherchkova T.A., Shkurat T.P.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/2186

Генетические полиморфизмы, которые влияют на эффективность репарации ДНК, потенциально могут быть связаны с заболеваниями, вызванными атеросклерозом. Мы определили подходящие исследования посредством всестороннего поиска литературы, чтобы определить, существует ли связь между полиморфизмами гена XRCC1 с такими заболеваниями, как ишемическая болезнь сердца (ИБС) и инфаркт, вызванными атеросклерозом. Результаты оценивались с использованием отношения шансов (ОШ) и соответствующего 95% доверительного интервала (ДИ), которые рассчитывались с использованием модели фиксированных или случайных эффектов на основе неоднородности исследований. Наконец, в этот мета-анализ были включены 6 подходящих исследований. Наш объединенный анализ показал, что полиморфизмы XRCC1 в значительной степени связаны с предрасположенностью к заболеваниям, вызванными атеросклерозом, при сравнении гомозигот (Arg194Trp в общей популяции: ОШ = 1,42, 95% ДИ = 1,07-1,89; Arg399Gln в европеоидной популяции: ОШ = 1,68, 95% ДИ = 1,07-2,63; Arg399Gln в общей популяции: ОШ = 1,46, 95% ДИ = 1,10-1,92) и в условиях доминантной генетической модели (Arg194Trp в общей популяции: ОШ = 0,66, 95% ДИ = 0,5-0,86; Arg399Gln в европеоидной популяции: ОШ = 0,65, 95% ДИ = 0,43-1,00; Arg399Gln в общей популяции: ОШ = 0,71, 95% ДИ = 0,54-0,93). На основании нашего мета-анализа мы пришли к выводу, что полиморфизмы гена XRCC1 Arg194Trp и Arg399Gln, могут быть связаны с ИБС и предрасположенностью к инсульту. Однако для подтверждения этих выводов необходимы дополнительные всесторонние исследования.

Genetic variations that influence DNA repair efficiency potentially may contribute to atherosclerosis-indused diseases susceptibility. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphism with such atherosclerosis-indused diseases as coronary artery disease (CAD) and infarct. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. 6 eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with atherosclerosis-indused diseases susceptibility in homozygote comparisons (Arg194Trp in a total population: OR = 1.42, 95% CI = 1.07-1.89; Arg399Gln in a Caucasian population: OR = 1.68, 95% CI = 1.07-2.63; Arg399Gln in a total population: OR = 1.46, 95% CI = 1.10-1.92) and under dominant genetic model (Arg194Trp in a total population: OR = 0.66, 95% CI = 0.5-0.86; Arg399Gln in a Caucasian population: OR = 0.65, 95% CI = 0.43-1.00; Arg399Gln in a total population: OR = 0.71, 95% CI = 0.54-0.93). Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, may be associated with CAD and stroke susceptibility. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.

ген XRCC1полиморфизматеросклерозмета-анализXRCC1polymorphismatherosclerosismeta-analysisReferencesGrootaert M.O., da Costa Martins P.A., Bitsch N., et al. Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherogenesis. Autophagy. 2015;11(11):2014-2032.Grootaert M.O., da Costa Martins P.A., Bitsch N., et al. Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherogenesis. Autophagy. 2015;11(11):2014-2032.Slimen I.B., Najar T., Ghram A., et al. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review.International journal of hyperthermia: the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2014;30(7):513-523.Slimen I.B., Najar T., Ghram A., et al. Reactive oxygen species, heat stress and oxidative-induced mitochondrial damage. A review.International journal of hyperthermia: the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group. 2014;30(7):513-523.Andreassi M.G. Coronary atherosclerosis and somatic mutations: an overview of the contributive factors for oxidative DNA damage. Mutation research. 2003;543(1):67-86.Andreassi M.G. Coronary atherosclerosis and somatic mutations: an overview of the contributive factors for oxidative DNA damage. Mutation research. 2003;543(1):67-86.Tiwari V., Wilson D.M.3rd. DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging. American journal of human genetics. 2019;105(2):237-257.Tiwari V., Wilson D.M.3rd. DNA Damage and Associated DNA Repair Defects in Disease and Premature Aging. American journal of human genetics. 2019;105(2):237-257.Klaunig JE. Oxidative Stress and Cancer. Current pharmaceutical design. 2018;24(40): 4771-4778.Klaunig JE. Oxidative Stress and Cancer. Current pharmaceutical design. 2018;24(40): 4771-4778.Wood R.D., Mitchell M., Sgouros J., Lindahl T. Human DNA repair genes. Science (New York, N.Y.). 2001;291(5507):1284-1289.Wood R.D., Mitchell M., Sgouros J., Lindahl T. Human DNA repair genes. Science (New York, N.Y.). 2001;291(5507):1284-1289.Lamerdin J.E., Montgomery M.A., Stilwagen S.A., et al. Genomic sequence comparison of the human and mouse XRCC1 DNA repair gene regions. Genomics. 1995;25(2):547-554.Lamerdin J.E., Montgomery M.A., Stilwagen S.A., et al. Genomic sequence comparison of the human and mouse XRCC1 DNA repair gene regions. Genomics. 1995;25(2):547-554.Shen M.R., Zdzienicka M.Z., Mohrenweiser H., et al. Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair. Nucleic acids research. 1998;26(4):1032-1037.Shen M.R., Zdzienicka M.Z., Mohrenweiser H., et al. Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair. Nucleic acids research. 1998;26(4):1032-1037.Sak S.C., Barrett J.H., Paul A.B., et al. DNA repair gene XRCC1 polymorphisms and bladder cancer risk. BMC genetics. 2007;8:13.Sak S.C., Barrett J.H., Paul A.B., et al. DNA repair gene XRCC1 polymorphisms and bladder cancer risk. BMC genetics. 2007;8:13.Moher D., Liberati A., Tetzlaff J., Altman D.G., PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS medicine. 2009;6(7):e1000097.Moher D., Liberati A., Tetzlaff J., Altman D.G., PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS medicine. 2009;6(7):e1000097.Higgins J.P., Thompson S.G., Deeks J.J., Altman D.G. Measuring inconsistency in meta-analyses. BMJ (Clinical research ed.). 2003;327(7414):557-560.Higgins J.P., Thompson S.G., Deeks J.J., Altman D.G. Measuring inconsistency in meta-analyses. BMJ (Clinical research ed.). 2003;327(7414):557-560.Guven M., Guven G.S., Oz E., et al. DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency. Heart and vessels. 2007;22(6):355-360.Guven M., Guven G.S., Oz E., et al. DNA repair gene XRCC1 and XPD polymorphisms and their association with coronary artery disease risks and micronucleus frequency. Heart and vessels. 2007;22(6):355-360.Shyu H.Y., Shieh J.C., Ji-Ho L., et al. Polymorphisms of DNA repair pathway genes and cigarette smoking in relation to susceptibility to large artery atherosclerotic stroke among ethnic Chinese in Taiwan. Journal of atherosclerosis and thrombosis. 2012;19(4):316-325.Shyu H.Y., Shieh J.C., Ji-Ho L., et al. Polymorphisms of DNA repair pathway genes and cigarette smoking in relation to susceptibility to large artery atherosclerotic stroke among ethnic Chinese in Taiwan. Journal of atherosclerosis and thrombosis. 2012;19(4):316-325.Gokkusu C., Cakmakoglu B., Dasdemir S., et al. Association between genetic variants of DNA repair genes and coronary artery disease. Genetic testing and molecular biomarkers. 2013;17(4):307-313.Gokkusu C., Cakmakoglu B., Dasdemir S., et al. Association between genetic variants of DNA repair genes and coronary artery disease. Genetic testing and molecular biomarkers. 2013;17(4):307-313.Yu X., Liu J., Zhu H., et al. Synergistic association of DNA repair relevant gene polymorphisms with the risk of coronary artery disease in northeastern Han Chinese. Thrombosis research. 2014;133(2):229-234.Yu X., Liu J., Zhu H., et al. Synergistic association of DNA repair relevant gene polymorphisms with the risk of coronary artery disease in northeastern Han Chinese. Thrombosis research. 2014;133(2):229-234.Skarpengland T., Laugsand L.E., Janszky I., et al. Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case-control study. The HUNT Study. DNA repair. 2015;28:21-27.Skarpengland T., Laugsand L.E., Janszky I., et al. Genetic variants in the DNA repair gene NEIL3 and the risk of myocardial infarction in a nested case-control study. The HUNT Study. DNA repair. 2015;28:21-27.He W., Huang P., Liu D., et al. Polymorphism of the XRCC1 Gene Is Associated with Susceptibility and Short-Term Recovery of Ischemic Stroke.International journal of environmental research and public health. 2016;13(10):1016.He W., Huang P., Liu D., et al. Polymorphism of the XRCC1 Gene Is Associated with Susceptibility and Short-Term Recovery of Ischemic Stroke.International journal of environmental research and public health. 2016;13(10):1016.Pahlavanneshan S., Ahmadi A., Boroumand M., et al. Association of -77T>C and Arg194trp polymorphisms of XRCC1 with risk of coronary artery diseases in Iranian population. Iran J Basic Med Sci. 2016;19(2):194-200. PMID: 27081465; PMCID: PMC4818368.Pahlavanneshan S., Ahmadi A., Boroumand M., et al. Association of -77T>C and Arg194trp polymorphisms of XRCC1 with risk of coronary artery diseases in Iranian population. Iran J Basic Med Sci. 2016;19(2):194-200. PMID: 27081465; PMCID: PMC4818368.Özbilüm N., Arslan S., Yanartaş M., et al. Arg399Gln Polymorphism of the XRCC1 Gene is Associated with Coronary Artery Disease in a Turkish Population. West Indian Med J. 2017;66(6):610.Özbilüm N., Arslan S., Yanartaş M., et al. Arg399Gln Polymorphism of the XRCC1 Gene is Associated with Coronary Artery Disease in a Turkish Population. West Indian Med J. 2017;66(6):610.Singh R.B., Mengi S.A., Xu Y.J., et al. Pathogenesis of atherosclerosis: A multifactorial process. Experimental & Clinical Cardiology. 2002;7(1):40.Singh R.B., Mengi S.A., Xu Y.J., et al. Pathogenesis of atherosclerosis: A multifactorial process. Experimental & Clinical Cardiology. 2002;7(1):40.Yu E., Calvert P.A., Mercer J.R., et al. Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation. 2013;128(7):702-712.Yu E., Calvert P.A., Mercer J.R., et al. Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation. 2013;128(7):702-712.Kattoor A.J., Pothineni N., Palagiri D., Mehta J.L. Oxidative Stress in Atherosclerosis. Current atherosclerosis reports. 2017;19(11):42.Kattoor A.J., Pothineni N., Palagiri D., Mehta J.L. Oxidative Stress in Atherosclerosis. Current atherosclerosis reports. 2017;19(11):42.Sena C.M., Pereira A.M., Seiça R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochimica et biophysica acta. 2013;1832(12):2216-2231.Sena C.M., Pereira A.M., Seiça R. Endothelial dysfunction - a major mediator of diabetic vascular disease. Biochimica et biophysica acta. 2013;1832(12):2216-2231.Victor V. M., Rocha M., Sola E., Banuls C., Garcia-Malpartida K., Hernandez-Mijares A. Oxidative stress, endothelial dysfunction and atherosclerosis. Current pharmaceutical design. 2009;15(26): 2988-3002.Victor V. M., Rocha M., Sola E., Banuls C., Garcia-Malpartida K., Hernandez-Mijares A. Oxidative stress, endothelial dysfunction and atherosclerosis. Current pharmaceutical design. 2009;15(26): 2988-3002.Caldecott K.W. XRCC1 protein; Form and function. DNA repair. 2019;81:102664.Caldecott K.W. XRCC1 protein; Form and function. DNA repair. 2019;81:102664.Kaur J., Sambyal V., Guleria K., et al. Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk. Clinical and experimental gastroenterology. 2020; 13:73-86.Kaur J., Sambyal V., Guleria K., et al. Association of XRCC1, XRCC2 and XRCC3 Gene Polymorphism with Esophageal Cancer Risk. Clinical and experimental gastroenterology. 2020; 13:73-86.Prathap L., Suganthirababu P. Estrogen Exposure and its influence in DNA Repair Genetic Variants in Breast Cancer Population. Biomedical and Pharmacology Journal. 2020;13(3):1321-1327.Prathap L., Suganthirababu P. Estrogen Exposure and its influence in DNA Repair Genetic Variants in Breast Cancer Population. Biomedical and Pharmacology Journal. 2020;13(3):1321-1327.Khosa T., Aslam S., Mustafa S., et al. Association of Single Nucleotide Polymorphisms in XRCC1 (194) and XPD (751) with Age-related cataract.International ophthalmology. 2018;38(3):1135-1146.Khosa T., Aslam S., Mustafa S., et al. Association of Single Nucleotide Polymorphisms in XRCC1 (194) and XPD (751) with Age-related cataract.International ophthalmology. 2018;38(3):1135-1146.Sujitha S.P., Kumar D.T., Doss C.G., et al. DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study. PloS one. 2016;11(1):e0147348.Sujitha S.P., Kumar D.T., Doss C.G., et al. DNA Repair Gene (XRCC1) Polymorphism (Arg399Gln) Associated with Schizophrenia in South Indian Population: A Genotypic and Molecular Dynamics Study. PloS one. 2016;11(1):e0147348.Sherchkova T.A., Grigoryan N.A., Amelina M.A., et al. Role of XRCC1, XPC, NBN gene polymorphisms in spermatogenesis. Gene Reports. 2021;24:101238.Sherchkova T.A., Grigoryan N.A., Amelina M.A., et al. Role of XRCC1, XPC, NBN gene polymorphisms in spermatogenesis. Gene Reports. 2021;24:101238.

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