2658-6533Research Results in Biomedicine2658-653310.18413/2313-8955-2018-4-4-0-31595GeneticsPopulation genetic characteristics and genetic epidemiological research of candidate genes associations with multifactorial diseasesPopulation genetic characteristics and genetic epidemiological research of candidate genes associations with multifactorial diseasesSorokinaInna N.SorokinaInna N.Sorokina@bsu.edu.ruRudyhNatal'ya A.RudyhNatal'ya A.rudyh@bsu.edu.ruBezmenovaIrina N.BezmenovaIrina N.lependina_bel@mail.ruPolyakovaIrina S.PolyakovaIrina S.20184400

Background: When studying associations of candidate genes with multifactorial diseases, the formation of samples for research is important. One of the factors that should be considered in the formation of samples for genetic-epidemiological research are regional features of the genetic structure of the population. The aim of the study: To study the factors of heterogeneity of the population-genetic structure of the population of southern Central Russia (Belgorod region) and assess their role in the planning of a genetic and epidemiological study of the population. Materials and methods: The genetic structure of the population of the Belgorod region was studied using autosomal DNA markers (8 loci — ApoB eNOS, CCR5, hSERT, D1S80, DAT1, PAH and АСЕ in 620 individuals of 4 districts); immunobiochemical gene markers (12 systems - ACP1, АВО, ESD, RH, HP, GC, PI, C’3, GLO1, PGM1, 6-PGD, TF in 582 individuals of 4 regions); Y-chromosome markers (20 diallel loci of the non-recombining part of the Y-chromosome: M1 (YAP), М9, М17, М46 (Tat), M70, M78, M170, M172, M173, M178, M201, M223, M231, M242, M253, М269, 12F2, Р37, P43, 92R7 and 7 STR markers: DYS385a/b, DYS388, DYS390, DYS391, DYS392, DYS393, DYS19 (DYS394) in 403 individuals of 5 districts) and quasi-genetic markers (48902 names among 822316 people area). The role of migration and the ethnic factor in the formation of the genetic heterogeneity of populations has been evaluated. Results: It has been established that migration and ethnicity are the major factors responsible for the genetic differences in the regional populations of the Central Black Soil Region. An increase in the influx of migrants results in a decrease in the level of division and the formation of heterogeneity of the population and genetic structure of people. The differences between the two ethnic groups of the population of the Belgorod region (Russians and Ukrainians) were revealed in the three alleles of the two systems of classical gene markers (ABO and GC); haplogroup E3b1 and DYS390*24, DYS19*13, DYS19*14 STR Y-chromosome loci. An analysis of genetic relationships has shown that the Russian population of the Belgorod Region is grouped together in an independent cluster, and the Ukrainian population of the region is genetically removed from it. Conclusion: Significant factors of population dynamics that affect the level of genetic diversity of the population are migration and ethnicity. Thus, in the formation of samples for medicogenetic and genetic-epidemiological studies of the population, it is necessary to take into account the place of birth of spouses and nationality.

Background: When studying associations of candidate genes with multifactorial diseases, the formation of samples for research is important. One of the factors that should be considered in the formation of samples for genetic-epidemiological research are regional features of the genetic structure of the population. The aim of the study: To study the factors of heterogeneity of the population-genetic structure of the population of southern Central Russia (Belgorod region) and assess their role in the planning of a genetic and epidemiological study of the population. Materials and methods: The genetic structure of the population of the Belgorod region was studied using autosomal DNA markers (8 loci — ApoB eNOS, CCR5, hSERT, D1S80, DAT1, PAH and АСЕ in 620 individuals of 4 districts); immunobiochemical gene markers (12 systems - ACP1, АВО, ESD, RH, HP, GC, PI, C’3, GLO1, PGM1, 6-PGD, TF in 582 individuals of 4 regions); Y-chromosome markers (20 diallel loci of the non-recombining part of the Y-chromosome: M1 (YAP), М9, М17, М46 (Tat), M70, M78, M170, M172, M173, M178, M201, M223, M231, M242, M253, М269, 12F2, Р37, P43, 92R7 and 7 STR markers: DYS385a/b, DYS388, DYS390, DYS391, DYS392, DYS393, DYS19 (DYS394) in 403 individuals of 5 districts) and quasi-genetic markers (48902 names among 822316 people area). The role of migration and the ethnic factor in the formation of the genetic heterogeneity of populations has been evaluated. Results: It has been established that migration and ethnicity are the major factors responsible for the genetic differences in the regional populations of the Central Black Soil Region. An increase in the influx of migrants results in a decrease in the level of division and the formation of heterogeneity of the population and genetic structure of people. The differences between the two ethnic groups of the population of the Belgorod region (Russians and Ukrainians) were revealed in the three alleles of the two systems of classical gene markers (ABO and GC); haplogroup E3b1 and DYS390*24, DYS19*13, DYS19*14 STR Y-chromosome loci. An analysis of genetic relationships has shown that the Russian population of the Belgorod Region is grouped together in an independent cluster, and the Ukrainian population of the region is genetically removed from it. Conclusion: Significant factors of population dynamics that affect the level of genetic diversity of the population are migration and ethnicity. Thus, in the formation of samples for medicogenetic and genetic-epidemiological studies of the population, it is necessary to take into account the place of birth of spouses and nationality.

polymorphismassociationsgene poolmigrationnationalitypolymorphismassociationsgene poolmigrationnationalityСписок литературыZinchenko R.A., Kadyshev V.V., El`chinova G.I., et al. Study of the load and diversity of hereditary diseases among the Russian population of the Karachay-Cherkess Republic. Medical Genetics. 2018;17(7):30-37. Russian. DOI: https://doi.org/10.25557/2073-7998.2018.07.30-37Zinchenko R.A., Kadyshev V.V., Galkina V.A., et al. Medical Genetic Study of Hereditary Diseases in Abazins of the Karachay-Cherkess Republic. Russian Journal of Genetics. 2018;54(6):703-711. DOI: 10.7868/S0016675818060097Moskalenko MI. The involvement of genes of matrix metalloproteinases in the development of arterial hypertension and its complication (review). Research Result. Medicine and Pharmacy. 2018;4(1):53-69. Russian. DOI: 10.18413/2313-8955-2018-4-1-53-69Rodríguez-Pérez JM, Vargas-Alarcón G, Posadas-Sánchez R, et al. rs3918242 MMP9 gene polymorphism is associated with myocardial infarction in Mexican patients. Genet Mol Res. 2016; № 15(1). DOI: 10.4238/gmr.15017776Morris DR, Biros E, Cronin O, et al. The association of genetic variants of matrix metalloproteinases with abdominal aortic aneurysm: a systematic review and meta-analysis. Heart. 2014;100(4):295-302. DOI: 10.1136/heartjnl-2013-304129Djuric T, Zivkovic M, Milosevic B, et al. MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract. Pediatr Nephrol. 2014;29(5):879-884. DOI: 10.1007/s00467-013-2699-xVelho FM, Cohen CR, Santos KG, et al. Polymorphisms of matrix metalloproteinases in systolic heart failure: role on disease susceptibility, phenotypic characteristics, and prognosis. J Card Fail. 2011;17(2):115-121. DOI: 10.1016/j.cardfail.2010.09.017Qintao C, Yan L, Changhong D, et al. Genetic polymorphism of matrix metalloproteinase-1 and coronary artery disease susceptibility: a case-control study in a Han Chinese population. Genet Test Mol Biomarkers. 2014;18(12):826-831. DOI: 10.1089/gtmb.2014.0222Lacchini R, Jacob-Ferreira AL, Luizon MR, et al.Common matrix metalloproteinase 2 gene haplotypes may modulate left ventricular remodelling in hypertensive patients. Hum Hypertens. 2012;26(3):171-177. DOI: 10.1038/jhh.2011.8Metzger IF, Luizon MR, Lacchini R, et al. Genetic variants in matrix metalloproteinase-9 gene modify metalloproteinase-9 levels in black subjects / I.F. Metzger [et al.] // DNA Cell Biol. 2012;31(4):504-510. DOI: 10.1089/dna.2011.1388Balanovskaya EV, Balanovsky OP. [Russian gene pool on the Russian plain]. M.: Luch; 2007. 416 p. Russian.Elchinova GI. [Experience of using population-genetic analysis methods in studying populations of Russia with different genetic and demographic structure] [dissertation]. Moscow: GU MGNTS RAMN; 2001. Russian.Еl'chinоvа GI, Rеvаzоvа YuА, Makaov AKh-M, et al. Pоpulatiоn and gеnеtiс characteristics of Nоgаis in Karachay-Cherkessia (by data abоut the surname distribution and marriage migration). Moscow University Bulletin. Series 23: Anthropology. 2016;1:109-115. Russian.Elchinova GI, Bikanov RA, Petrin AN, et al. Russians of the Karachay-Cherkess Republic: population genetic portrait. Russian Journal of Genetics. 2018;54(9):1117-1119. Russian.Kurbatova OL, Yankovsky NK. Migration as the main factor of the russias urban population dynamics. Russian Journal of Genetics. 2016;52(7):726-745. Russian.  DOI: 10.7868/S0016675816070067Balanovska EV, Agdzhoyan AT, Skhalyakho RA, et al. Gene pool of the Novgorod population: between the north and the south. Russian Journal of Genetics. 2017;53(11):1338-1348. Russian. DOI: 10.7868/S0016675817110029 Rudyh NA, Sirotina SS. Genetic interrelations of Russian and Ukrainian populations of the Belgorod region. Research Result. Medicine and Pharmacy. 2015;1(3(5)):72-79. Russian. DOI: 10.18413/2313-8955-2015-1-3-72-79Rudykh NA. [Studying the structure of the gene pool of the population of the Belgorod region and its place in the East Slavic gene pool system (according to data on autosomal DNA polymorphism)] [dissertation]. Belgorod; 2009. Russian.Lependina IN. [Genetic structure of the Belgorod population and its position in the system of the East Slavic gene pool (according to data on immuno-biochemical gene markers)] [dissertation]. Belgorod; 2005. Russian.Tsapkova LA. [Polymorphism of the Y-chromosome among the population of the Belgorod region] [dissertation]. Belgorod; 2008. Russian.Sorokina IN, Churnosov MI, Balanovska EV. The gene pool of the Belgorod region population: I. Differentiation of all district populations based on anthroponymic data. Russian Journal of Genetics. 2007;43(6):697-704. Russian.[Internet]. Place: Belgorod; [cited 2018 Oct 9]. Available from: http://belg.gks.ru RussianSorokina IN, Churnosov MI, Balanovska EV. The gene pool of the Belgorod region population: description of the "genetic landscape" of 22 district populations. Journal of Genetics. 2009;45(5):613-622. Russian.