medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.10.30-37medgen-2557Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРаспространенность вариантов гена эксцизионной репарации оснований ДНК среди восточных хантовThe prevalence of DNA base excision repair gene variants among the Eastern Khants populationМакаровС. В.MakarovS. V.

 Макаров Сергей Вячеславович

115522, г. Москва,  ул. Москворечье, д. 1

 Sergey V. Makarov

1, Moskvorechye st., Moscow, 115522

ecolab@med-gen.ruСпицынВ. А.SpitsynV. A.

 115522, г. Москва,  ул. Москворечье, д. 1

1, Moskvorechye st., Moscow, 115522

СпицынаН. Х.SpitsynaN. Kh.

119334, г. Москва,  Ленинский просп., д. 32А

32A, Leninsky Prospekt, Moscow, 119334

ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»РоссияResearch Centre for Medical GeneticsRussian FederationЦентр физической антропологии, Институт этнологии и антропологии имени Н.Н. Миклухо-Маклая Российской акадекмии наукРоссияCentre for Physical Anthropology, Miklukho-Maclay Institute of Ethnology and Anthropology Russian Academy of SciencesRussian Federation20240512202423103037Copyright © Макаров С.В., Спицын В.А., Спицына Н.Х., 20242024Макаров С.В., Спицын В.А., Спицына Н.Х.Makarov S.V., Spitsyn V.A., Spitsyna N.K.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/2557Введение

Введение. Проблема сохранения здоровья населения северных регионов Евразии имеет приоритетную важность, особенно в отношении малочисленных коренных народов и в связи с интенсификацией антропогенного воздействия на окружающую среду. Жизнеспособность организма во многом зависит от наличия эффективных защитных средств против неблагоприятных факторов. У человека основным элементом одной из таких систем – эксцизионной репарации оснований ДНК – является 8-оксогуанин-ДНК-гликозилаза (OGG1), противостоящая неблагоприятным последствиям оксидативного стресса. В популяциях человека ген OGG1 имеет вариации в кодирующей последовательности, частоты встречаемости которых могут различаться в разных этнических группах. Замена аминокислотного остатка Ser326Cys снижает эффективность репарационной функции и носительство такой мутации, особенно в гомозиготном состоянии, чревато повышенным риском канцерогенеза и некоторыми другими неблагоприятными последствиями для здоровья.

Цель

Цель: установление частот встречаемости аллелей и генотипов полиморфизма rs1052133 гена OGG1, связанного с эксцизионной репарацией оснований, в популяции восточных хантов и сопоставление характера распределения с распространенностью в других популяциях Земного шара.

Методы

Методы. Выборка восточных хантов состояла из 103 коренных жителей Ханты-Мансийского автономного округа. Генотипирование по полиморфизму Ser326Cys в экзоне 7 гена OGG1 (rs1052133) проводилось методом ARMS-PCR-RFLP .

Результаты

Результаты. В изученной популяции частота генотипа Ser/Ser составила 47,6%, Ser/Cys – 36,9 % , Cys/Cys – 15,5 %. Частота аллеля OGG1*С (Ser) оказалась равной 0,66, а OGG1*G (Cys) достигла значения 0,34.

Вывод

Вывод. Результаты исследования представляют новую популяционно-генетическую информацию о распространенности вариантов гена OGG1 в популяции хантов. Частоты аллелей оказались близки к средним относительно мировой вариации.

Background

Background. The healthcare has the priority importance for the Northern Eurasia indigenous populations survival. The organism viability largely depends on the availability of effective protective systems against adverse factors. The one is 8-oxoguanine DNA glycosylase (OGG1) which help to resist against the adverse effects of oxidative stress.

The human OGG1 gene has coding sequence variations which may differ in different ethnic groups. The Ser326Cys mutation reduces the effectiveness of the DNA repair function and it causes an increased risk of carcinogenesis and some other adverse health consequences.

Objective

Objective: to estimate the prevalence OGG1 gene variants among the indigenous Khants population and to compare it with different ethnic groups worldwide.

Methods

Methods. The sample of Eastern Khants consisted of 103 indigenous inhabitants of the Khanty-Mansiysk Autonomous Okrug. OGG1 gene Ser326Cys polymorphism genotyping (rs1052133) was performed using the ARMS-PCR-RFLP method.

Results

Results. The frequency stated for Ser/Ser genotype was 47.6%, Ser/Cys = 36.9 % and Cys/Cys = 15.5% in the Khants population. Frequency of the OGG1 allele*C (Ser) was equal to 0.66, and OGG1*G (Cys) reached the value of 0.34. .

Conclusion

Conclusion. The results of the study provide new population-genetic information on the prevalence of variants of the OGG1 gene. The frequencies of the rs1052133 alleles in the Khants population were close to the global average values.

эксцизионная репарациявосточные хантыOGG1rs1052133Ser326CysполиморфизмBERKhants populationOGG1rs1052133Ser326CyspolymorphismРабота выполнена в рамках государственного задания Минобрнауки России.The study has been funded by the state assignment of the Ministry of Science and Higher Education of the Russian FederationReferencesKohno 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.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.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.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 DNArepair gene variants on the micronucleus frequency in thyroid cancer patients. Mutation research. 2013;750(1-2):34-39.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.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.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.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.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 openangle glaucoma. Mutation research. 2013;753(1):12-22.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.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.Спицына Н.Х., Макаров С.В., Бец Л.В. et al. Новая информация о генофонде восточных хантов . Вестник Московского университета.Серия 23: Антропология. 2014;(4):101-106.Spitsyna N.Kh., Makarov S.V., Bets L.V. et al. Novaja informacija o genofonde vostochnyh hantov [New information about gene pool of eastern Khants] Vestnik Moskovskogo universiteta.Serija XXIII. Antropologija. [Moscow University Anthropology Bulletin] 2014;(4):101-106. (In Russ.)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.Efron B. The jackkife, the bootstrap, and other resampling plans. CBMS-NSF.Regional conference series in applied mathematics. 1982;38:27-36.Efron B. The jackkife, the bootstrap, and other resampling plans. CBMS-NSF.Regional conference series in applied mathematics. 1982;38:27-36.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.Макаров С.В., Квеквескири K.Б. Распространенность вариантов гена эксцизионной репарации оснований ДНК среди коренного населения Абхазии. Медицинская генетика. 2021;20(9):26-33.Makarov S.V., Kvekveskiri K.B. Rasprostranennost’ variantov gena jekscizionnoj reparacii osnovanij DNK sredi korennogo naselenija Abhazii. [The prevalence of DNA base excision repair gene variants among the indigenous Abkhazian population] Medicinskaja genetika [Medical genetics] 2021;20(9):26-33. (In Russ.)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 BaseExcision 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.Neel G.J., Schull W.J. Human Heredity.University of Chicago Press. 1954. -361.Neel G.J., Schull W.J. Human Heredity.University of Chicago Press. 1954. -361.Pimenoff V.N., Comas D., Palo J.U. et al. Northwest Siberian Khanty and Mansi in the junction of West and East Eurasian gene pools as revealed by uniparental markers. Eur.J.Hum.Genet. 2008;16(10):1254- 1264.Pimenoff V.N., Comas D., Palo J.U. et al. Northwest Siberian Khanty and Mansi in the junction of West and East Eurasian gene pools as revealed by uniparental markers. Eur.J.Hum.Genet. 2008;16(10):1254-1264.Naumova O.I., Khaiat S.S., Rychkov S.I. Mitochondrial DNA diversity in Kazym Khanty. Genetika. 2009;45(6):857-861.Naumova O.I., Khaiat S.S., Rychkov S.I. Mitochondrial DNA diversity in Kazym Khanty. Genetika. 2009;45(6):857-861.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.Makarov S.V., Karapetian M.K. K gipoteze o svjazi polimorfizma ABCC11 i opuholi molochnoj zhelezy. Etnicheskij aspekt. [On the hypothesis of an association between ABCC11 polymorphism and breast cancer. Ethnic aspect] Medicinskaja genetika [Medical genetics] 2020;19(6):33-35. (In Russ.)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):5155-5163Kudhair 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

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