medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2021.09.26-33medgen-1975Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРаспространенность вариантов гена эксцизионной репарации оснований ДНК среди коренного населения АбхазииThe prevalence of DNA base excision repair gene variants among the indigenous Abkhazian populationМакаровС. В.MakarovS. V.ecolab@med-gen.ruКвеквескириК. Б.KvekveskiriK. B.noemail@neicon.ruФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian FederationАбхазский государственный университетРоссияAbkhazian State UniversityRussian Federation2021091220212092633Copyright © Макаров С.В., Квеквескири К.Б., 20212021Макаров С.В., Квеквескири К.Б.Makarov S.V., Kvekveskiri K.B.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/1975

Актуальность. Загрязнение окружающей среды промышленными отходами, токсическими агентами, опасными излучениями обусловливает возрастание мутационных процессов в биосфере, повреждений ДНК в клетках, рисков онкологических заболеваний. Жизнеспособность организма во многом зависит от наличия эффективных защитных средств против таких неблагоприятных факторов. Невозможность избежать повреждающих ДНК факторов экзогенного и эндогенного характера привела к возникновению более или менее эффективных репарационных систем, суть которых - элиминация первичных повреждений до их воплощения в мутационные события. У человека основным элементом одной из таких систем - эксцизионной репарации оснований ДНК является 8-оксогуанин-ДНК-гликозилаза (OGG1), противостоящая неблагоприятным последствиям оксидативного стресса. Ген OGG1 имеет вариации в кодирующей последовательности, частоты встречаемости которых могут различаться в разных этнических группах, но различаться может и эффективность функционирования продукта трансляции с такого транскрипта. Ser326Cys - яркий тому пример, замена аминокислотного остатка снижает эффективность репарационной функции, и носительство такой мутации, особенно в гомозиготном состоянии, чревато повышенным риском канцерогенеза и некоторыми другими неблагоприятными последствиями для здоровья. Цель. Исследование было направлено на установление частот встречаемости аллелей и генотипов полиморфизма rs1052133 гена OGG1, связанного с эксцизионной репарацией оснований, в популяции абхазов и сопоставление характера распределения с распространенностью в других популяциях Земного шара. Методы. В выборку для исследования абхазской популяции было включено 168 коренных жителей, постоянно проживающих на территории Абхазии. Генотипирование по полиморфизму Ser326Cys в экзоне 7 гена OGG1 (rs1052133) производилось методом ARMS-PCR-RFLP . Результаты. В выборке из абхазской популяции частота генотипа Ser/Ser составила 44,1%, Ser/Cys - 49,4 %, Cys/Cys - 6,5%. Частота аллеля OGG1*С (Ser) оказалась равной 0,688, а OGG1*G (Cys) достигла значения 0,312. Вывод. Частоты аллелей этого полиморфизма в популяции абхазов оказались близки к глобальным среднемировым значениям.

Background. Environmental pollutions, toxic agents and dangerous radiation lead to increasing in levels of mutational processes, DNA damages and higher risks of cancer for bioorganisms. The life system viability depends on the effectiveness of the neutralizing the adverse factors. The unavoidance of the DNA damaging factors has led to developing the effective repair systems aimed to eliminate the primary damage. 8-oxoguanine-DNA glycosylase (OGG1) is the major element of the Base Excision Repair (BER) in human. The OGG1 gene has coding sequence variations spread with different frequencies in human populations. Ser326Cys is SNP with known defect in DNA repairing for Cys-allelomorph and an increased risk of cancer in the case. Objective. The study was aimed to estimate the prevalence OGG1 gene variants among the indigenous Abkhazian population and comparison with different ethnic groups worldwide. Methods. The study based on the analysis of 168 samples from Abkhazians. The OGG1 gene Ser326Cys genotyping was performed by the ARMS-PCR-RFLP . Results. The frequency stated for Ser/Ser genotype was 44.1%, Ser/Cys = 49.4 % and Cys/Cys = 6.5% in the Abkhazian population. Frequency of the OGG1 allele*C (Ser) was equal to 0.688, and OGG1*G (Cys) reached the value of 0.312. Conclusion. The frequencies of the rs1052133 alleles in the Abkhazian population were close to the global average values.

OGG1rs1052133Ser326Cysполиморфизмабхазыэксцизионная репарацияOGG1rs1052133Ser326CyspolymorphismAbkhazian populationBERReferencesKohno T., Shinmura K., Tosaka M. et al. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16(25):3219-3225.Kohno T., Shinmura K., Tosaka M. et al. Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene. 1998;16(25):3219-3225.Wei W., He X.F., Qin J.B. et al. Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis. Molecular biology reports. 2012;39(12):11249-11262.Wei W., He X.F., Qin J.B. et al. Association between the OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and lung cancer risk: a meta-analysis. Molecular biology reports. 2012;39(12):11249-11262.Liu C., Huang H., Wang C. et al. Association between OGG1 gene single nucleotide polymorphisms and risk of pancreatic cancer in Chinese. Medical oncology (Northwood, London, England). 2014;31(7):40.Liu C., Huang H., Wang C. et al. Association between OGG1 gene single nucleotide polymorphisms and risk of pancreatic cancer in Chinese. Medical oncology (Northwood, London, England). 2014;31(7):40.Peng Q., Lu Y., Lao X. et al. Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis. Diagnostic pathology. 2014;9:108.Peng Q., Lu Y., Lao X. et al. Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis. Diagnostic pathology. 2014;9:108.Arcand S.L., Provencher D., Mes-Masson A.M. et al. OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer. International journal of oncology. 2005;27(5):1315-1320.Arcand S.L., Provencher D., Mes-Masson A.M. et al. OGG1 Cys326 variant, allelic imbalance of chromosome band 3p25.3 and TP53 mutations in ovarian cancer. International journal of oncology. 2005;27(5):1315-1320.Zengi A., Karadeniz M., Cetintas V.B. et al. Is there any association between the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene and risk of colon polyp and abnormal glucose tolerance in acromegaly patients? Genetic testing and molecular biomarkers. 2013;17(4):267-273.Zengi A., Karadeniz M., Cetintas V.B. et al. Is there any association between the Ser326Cys polymorphism of the 8-oxoguanine glycosylase 1 (OGG1) gene and risk of colon polyp and abnormal glucose tolerance in acromegaly patients? Genetic testing and molecular biomarkers. 2013;17(4):267-273.Takezaki T., Gao C.M., Wu J.Z. et al. hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese. International journal of cancer. 2002;99(4):624-627.Takezaki T., Gao C.M., Wu J.Z. et al. hOGG1 Ser(326)Cys polymorphism and modification by environmental factors of stomach cancer risk in Chinese. International journal of cancer. 2002;99(4):624-627.Smal M.P., Kuzhir T.D., Savina N.V. et al. BER gene polymorphisms associated withВ keyВ molecular events in bladder cancer. Experimental oncology. 2018;40(4):288-298.Smal M.P., Kuzhir T.D., Savina N.V. et al. BER gene polymorphisms associated withВ keyВ molecular events in bladder cancer. Experimental oncology. 2018;40(4):288-298.Garcia-Quispes W.A., Pastor S., Galofre P. et al. Influence of DNA-repair gene variants on the micronucleus frequency in thyroid cancer patients. Mutation research. 2013;750(1-2):34-39.Garcia-Quispes W.A., Pastor S., Galofre P. et al. Influence of DNA-repair gene variants on the micronucleus frequency in thyroid cancer patients. Mutation research. 2013;750(1-2):34-39.Grundmark B., Zethelius B., Garmo H. et al. Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up. BMC cancer. 2011;11:431.Grundmark B., Zethelius B., Garmo H. et al. Serum levels of selenium and smoking habits at age 50 influence long term prostate cancer risk; a 34 year ULSAM follow-up. BMC cancer. 2011;11:431.Pao P.C., Patnaik D., Watson L.A. et al. HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease. Nature communications. 2020;11(1):2484.Pao P.C., Patnaik D., Watson L.A. et al. HDAC1 modulates OGG1-initiated oxidative DNA damage repair in the aging brain and Alzheimer’s disease. Nature communications. 2020;11(1):2484.Gotoh N., Saitoh T., Takahashi N. et al. Association between OGG1 S326C CC genotype and elevated relapse risk in acute myeloid leukemia. International journal of hematology. 2018;108(3):246-253.Gotoh N., Saitoh T., Takahashi N. et al. Association between OGG1 S326C CC genotype and elevated relapse risk in acute myeloid leukemia. International journal of hematology. 2018;108(3):246-253.Hassan F.M. OGG1 rs1052133 Polymorphism and Genetic Susceptibility to Chronic Myelogenous Leukaemia. Asian Pacific journal of cancer prevention : APJCP. 2019;20(3):925-928.Hassan F.M. OGG1 rs1052133 Polymorphism and Genetic Susceptibility to Chronic Myelogenous Leukaemia. Asian Pacific journal of cancer prevention : APJCP. 2019;20(3):925-928.Daimon M., Oizumi T., Toriyama S. et al. Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM. Biochemical and biophysical research communications. 2009;386(1):26-29.Daimon M., Oizumi T., Toriyama S. et al. Association of the Ser326Cys polymorphism in the OGG1 gene with type 2 DM. Biochemical and biophysical research communications. 2009;386(1):26-29.Karahalil B., Orhan G., Ak F. The impact of detoxifying and repair gene polymorphisms and the levels of serum ROS in the susceptibility to multiple sclerosis. Clinical neurology and neurosurgery. 2015;139:288-294.Karahalil B., Orhan G., Ak F. The impact of detoxifying and repair gene polymorphisms and the levels of serum ROS in the susceptibility to multiple sclerosis. Clinical neurology and neurosurgery. 2015;139:288-294.Gharib A.F., Dabour S.A., Etewa R.L. et al. Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians. Molecular vision. 2014;20:661-669.Gharib A.F., Dabour S.A., Etewa R.L. et al. Polymorphisms of DNA repair genes OGG1 and XPD and the risk of age-related cataract in Egyptians. Molecular vision. 2014;20:661-669.Szaflik J.P., Cuchra M., Przybylowska-Sygut K. et al. Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma. Mutation research. 2013;753(1):12-22.Szaflik J.P., Cuchra M., Przybylowska-Sygut K. et al. Association of the 399Arg/Gln XRCC1, the 194 Arg/Trp XRCC1, the 326Ser/Cys OGG1, and the 324Gln/His MUTYH gene polymorphisms with clinical parameters and the risk for development of primary open-angle glaucoma. Mutation research. 2013;753(1):12-22.Garcia-Rodriguez A., de la C.M., Serrano M. et al. Impact of polymorphism in DNA repair genes OGG1 and XRCC1 on seminal parameters and human male infertility. Andrologia. 2018;50(10):e13115.Garcia-Rodriguez A., de la C.M., Serrano M. et al. Impact of polymorphism in DNA repair genes OGG1 and XRCC1 on seminal parameters and human male infertility. Andrologia. 2018;50(10):e13115.Corella D., Ramirez-Sabio J.B., Coltell O. et al. Effects of the Ser326Cys Polymorphism in the DNA Repair OGG1 Gene on Cancer, Cardiovascular, and All-Cause Mortality in the PREDIMED Study: Modulation by Diet. Journal of the Academy of Nutrition and Dietetics. 2018;118(4):589-605.Corella D., Ramirez-Sabio J.B., Coltell O. et al. Effects of the Ser326Cys Polymorphism in the DNA Repair OGG1 Gene on Cancer, Cardiovascular, and All-Cause Mortality in the PREDIMED Study: Modulation by Diet. Journal of the Academy of Nutrition and Dietetics. 2018;118(4):589-605.Kaur K., Kaur R. Impact of single nucleotide polymorphisms in the OGG1 and XRCC1 genes on modulation of DNA damage in pesticide-exposed agricultural workers in Punjab, North-West India. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 2020;25(6):498-505.Kaur K., Kaur R. Impact of single nucleotide polymorphisms in the OGG1 and XRCC1 genes on modulation of DNA damage in pesticide-exposed agricultural workers in Punjab, North-West India. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 2020;25(6):498-505.Макаров С.В., Карапетян М.К., Квеквескири К.Б. et al. Исследование полиморфизмов плейотропных генов ABCC11 и ACE в популяции абхазов и феномен долгожительства. Медицинская генетика. 2019;18(8):29-36.Макаров С.В., Карапетян М.К., Квеквескири К.Б. et al. Исследование полиморфизмов плейотропных генов ABCC11 и ACE в популяции абхазов и феномен долгожительства. Медицинская генетика. 2019;18(8):29-36.Nei M., Tajima F., Tateno Y. Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data. Journal of molecular evolution. 1983;19(2):153-170.Nei M., Tajima F., Tateno Y. Accuracy of estimated phylogenetic trees from molecular data. II. Gene frequency data. Journal of molecular evolution. 1983;19(2):153-170.Lai C.Y., Hsieh L.L., Tang R. et al. Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan. World journal of gastroenterology. 2016;22(12):3372-3380.Lai C.Y., Hsieh L.L., Tang R. et al. Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan. World journal of gastroenterology. 2016;22(12):3372-3380.Kim K.Y., Han W., Noh D.Y. et al. Impact of genetic polymorphisms in base excision repair genes on the risk of breast cancer in a Korean population. Gene. 2013;532(2):192-196.Kim K.Y., Han W., Noh D.Y. et al. Impact of genetic polymorphisms in base excision repair genes on the risk of breast cancer in a Korean population. Gene. 2013;532(2):192-196.Pramanik S., Surendran S.T., Arumugam S. et al. Polymorphisms in DNA repair and multidrug resistance genes among Sindhis of Central India. Environmental toxicology and pharmacology. 2015;40(2):480-485.Pramanik S., Surendran S.T., Arumugam S. et al. Polymorphisms in DNA repair and multidrug resistance genes among Sindhis of Central India. Environmental toxicology and pharmacology. 2015;40(2):480-485.Alanazi M., Pathan A.A., Ajaj S.A. et al. DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia. Biological research. 2013;46(2):161-167.Alanazi M., Pathan A.A., Ajaj S.A. et al. DNA Repair Genes XRCC1, XRCC3, XPD, and OGG1 Polymorphisms among the Central Region Population of Saudi Arabia. Biological research. 2013;46(2):161-167.Gonul N., Kadioglu E., Kocabas N.A. et al. The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population. Gene. 2012;505(1):121-127.Gonul N., Kadioglu E., Kocabas N.A. et al. The role of GSTM1, GSTT1, GSTP1, and OGG1 polymorphisms in type 2 diabetes mellitus risk: a case-control study in a Turkish population. Gene. 2012;505(1):121-127.Mandal R.K., Mittal T., Kapoor R. et al. NER and BER repair gene polymorphisms in a healthy north Indian cohort and comparison with different ethnic groups worldwide. Asian Pacific journal of cancer prevention : APJCP. 2010;11(6):1601-1604.Mandal R.K., Mittal T., Kapoor R. et al. NER and BER repair gene polymorphisms in a healthy north Indian cohort and comparison with different ethnic groups worldwide. Asian Pacific journal of cancer prevention : APJCP. 2010;11(6):1601-1604.Couto P.G., Bastos-Rodrigues L., Carneiro J.G. et al. DNA Base-Excision Repair Genes OGG1 and NTH1 in Brazilian Lung Cancer Patients. Molecular diagnosis & therapy. 2015;19(6):389-395.Couto P.G., Bastos-Rodrigues L., Carneiro J.G. et al. DNA Base-Excision Repair Genes OGG1 and NTH1 in Brazilian Lung Cancer Patients. Molecular diagnosis & therapy. 2015;19(6):389-395.Hosseini S.M., Mohammadiasl J., Talaiezadeh A. et al. Influence of Two DNA Repair Pathway Polymorphisms in Colorectal Cancer Risk in Southwest Iran. Asian Pacific journal of cancer prevention : APJCP. 2020;21(7):1919-1924.Hosseini S.M., Mohammadiasl J., Talaiezadeh A. et al. Influence of Two DNA Repair Pathway Polymorphisms in Colorectal Cancer Risk in Southwest Iran. Asian Pacific journal of cancer prevention : APJCP. 2020;21(7):1919-1924.Auton A., Brooks L.D., Durbin R.M. et al. A global reference for human genetic variation. Nature. 2015;526(7571):68-74.Auton A., Brooks L.D., Durbin R.M. et al. A global reference for human genetic variation. Nature. 2015;526(7571):68-74.Kudhair B.K., Alabid N.N., Zayed K.S. et al. The correlation of combined OGG1, CYP1A1 and GSTP1 gene variants and risk of lung cancer of male Iraqi waterpipe tobacco smokers. Molecular biology reports. 2020;47(7):5155-5163.Kudhair B.K., Alabid N.N., Zayed K.S. et al. The correlation of combined OGG1, CYP1A1 and GSTP1 gene variants and risk of lung cancer of male Iraqi waterpipe tobacco smokers. Molecular biology reports. 2020;47(7):5155-5163.Макаров С.В., Карапетян М.К. К гипотезе о связи полиморфизма ABCC11 и опухоли молочной железы. Этнический аспект. Медицинская генетика. 2020;19(6):33-35.Макаров С.В., Карапетян М.К. К гипотезе о связи полиморфизма ABCC11 и опухоли молочной железы. Этнический аспект. Медицинская генетика. 2020;19(6):33-35.

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