Determination of the chromosome aberrations frequency and the dynamics of acrocentric chromosomes associations in children with type I diabetes

Authors

  • R. F. Yeromenko National University of Pharmacy, Kharkіv, Ukraine,
  • V. I. Kovalova National University of Pharmacy, Kharkiv, Ukraine,
  • O. M. Lytvynova National University of Pharmacy, Kharkiv, Ukraine,
  • O. O. Palamarchuk National University of Pharmacy, Kharkiv, Ukraine,
  • V. S. Lytvynov V. N. Karazin Kharkiv National University, Ukraine,

DOI:

https://doi.org/10.14739/2310-1210.2018.5.141719

Keywords:

type 1 diabetes, chromosome aberrations, polyploidy, aneuploidy

Abstract

To date, it’s known that in Ukraine there are about 1 million patients with diabetes, but their real number is 2–3 times more, since this disease is usually diagnosed at the stage of already manifested pathological process. Unfortunately, diabetes mellitus remains an incurable disease, but it is possible to prolong life of patients or improve its quality by preventing or delaying its complications.

Objective. To study quantitative and qualitative cytogenetic indices in peripheral blood lymphocytes of children with type 1 diabetes mellitus.

Materials and methods. Cytogenetic study was performed in 30 children with type 1 diabetes aged from 5 to 17 years and 40 practically healthy peers.

Associations of acrocentric chromosomes (AAX) were evaluated using criteria developed by K. D. Zang and E. Back (1968). Metaphase plate analysis was performed using a Leica Galen III binocular microscope (Austria), an eyepiece of ×15, a lens of ×100, a binocular nozzle of ×1.25. The statistical processing of the results was carried out using Excel application packages, SPSS Statistica17.0.

Results: Changes in the somatic cells genome stability of children with type 1 diabetes have been revealed. Thus, the spontaneous level of chromosomal aberrations in the main and control groups was within 3.66 % and 0.96 %, respectively, and significantly exceeded the control indices (P < 0.005). In children, genomic abnormalities in the form of polyploidy and hypoploidy, as well as a decrease in CL0+2, were found, which indicates a decrease in the immunoreactivity of the sick children organism and allows to consider them as persons with secondary immunodeficiency.

Conclusions: The spontaneous level of chromosomal aberrations in peripheral blood lymphocytes in children with type 1 diabetes significantly exceeded the control indices. Cytogenetic examination of children with type 1 diabetes has revealed genomic disorders in the form of polyploid cells, which have not been detected in the control group. Changes in the genome stability in the form of hypoploid aneuploidy have also been found in the examined group. In children with type 1 diabetes a decrease in the acrocentric chromosomes ability to join associations has been identified, which makes it possible to consider these children as persons with secondary immunodeficiency.

 

References

Shestakova, M. V. (2010). Rasshirenie gruppy preparatov, osnovannykh na dejstvii genkretinov: novyi ingibitor DDP – 4 saksagliptin [Extension of a group of drugs based on the action of genkretin: a new inhibitor of DDP-4 saxagliptin]. Problemy e'ndokrinologii, 56(5), 52–60. [in Russian].

Nikonova, T. P. (2011). Sakharnyi diabet 1-go tipa i latentnyj autoimmunnyj diabet vzroslykh (LADA): klinicheskie, immunologicheskie i gormonal'no-metabolicheskie aspekty [Diabetes type 1 and latent autoimmune diabetes of adults (LADA): clinical, immunological and hormone-metabolic aspects]. Mezhdunarodnyj e'ndokrinologicheskij zhurnal, 7(39). Retrievrd from http://www.mif-ua.com/archive/article/22986. [in Russian].

Budreyko, O. A., Mykhailova, E. A., Kyrylova, O. O., et al. (2015). Psykholohichni aspekty samokontroliu tsukrovoho diabetu u ditei [Psychological aspects of self-control of diabetes in children]. Kyiv: Liudy u bilomu. [in Ukrainian].

Budreyko, O. A., Morozov, A. V., & Chumak, S. A. (2015). Kharakterystyka sertsevo-sudynnoi systemy dіtei, khvorykh na tsukrovyi dіabet i typy, zalezhno vіd rіvnia fіzychnoi aktyvnostі [Characteristics of the cardiovascular system of children with diabetes type I, depending on the level of physical activity]. Ukrainskyi zhurnal dytiachoi endokrynolohii, 2, 28–35. [in Ukrainian].

Ivanova, O. N., Stepanova, S. M., Smirnova, N. B., et al. (2014). Dimorfizm -23 HphI gena INS (rs689): associaciya s sakharnym diabetom 1-go tipa v populyaciyakh RF, mezhpopulyacionnoe sravnenie chastot [Dimorphism-23 HphI gene INS (rs689): association with type 1 diabetes mellitus in RF populations, interpopulation comparison of frequencies]. Problemy e'ndokrinologii, 6, 4–11. [in Russian].

Voronko, O. S., Bodaev, N. V., & Archakov, A. I. (2007). Ispol'zovanie SNP-markerov dlya ocenki individual'noj geneticheskoj predraspolozhennosti k sakharnomu diabetu tipa 1 i 2 [The use of SNP markers for estimation of individual genetic predisposition to diabetes mellitus type 1 and 2]. Biomedicinskaya khimiya, 53(4), 373–384. [in Russian].

Skudaev, S. A., & Verbovaya, N. I. (2011). E'ffektivnost' primeneniya insulina glargin v usloviyakh real'noj klinicheskoj praktiki: rezul'taty nabliudenij programmy LAURUS – 2 [The effectiveness of insulin glargine in the conditions of real clinical practice: the results of observations of the program LAURUS – 2]. Problemy e'ndokrinologii, 6, 15–20. [in Russian].

Emelyanov, A. O., Kuraeva, T. L., Prokofiev, S. A., Medvedeva, E. D., & Peterkova, V. A. (2014). Neonatal'nyj sakharnyj diabet: e'ffektivnost' terapii preparatami sul'fonilmocheviny v zavisimosti ot tipa mutacij v gene KCNJ11 [Neonatal diabetes mellitus: the effectiveness of therapy with sulfonylurea preparations depending on the type of mutation in the KCNJ11 gene]. Problemy e'ndokrinologii, 60(1), 57–63. [in Russian]. doi: 10.14341/probl201460157-63.

Titovich, E. V. (2011). Molekulyarno-geneticheskie, immunologicheskie osnovy i perspektivy profilaktiki sakharnogo diabeta u detej [Molecular-genetic, immunological bases and prophylaxis of diabetes mellitus in children]. Problemy e'ndokrinologii, 57(1), 9–18. [in Russian].

Chaychenko, T. V., Rybka, О. S., Buginska, N. R., Shulga, N. V., & Lutay, T. V. (2016). Dinamika koncentracii insulina i glyukozy krovi posle standartnoj peroral'noj uglevodnoj nagruzki u podrostkov s normal'noj, nedostatochnoj i izbytochnoj massoj tela [The dynamics of blood glucose and insulin concentration after the standard oral glucose tolerance test in overweight, underweight and normal weight adolescents]. Ukrainskyi zhurnal dytiachoi endokrynolohii, 2, 24–31. [in Russian].

Levenec, S. A. (2014). Insulinorezistentnost' pri rasstrojstvakh menstrual'noj funkcii u devochek-podrostkov [Insulin resistance in menstrual disorders in adolescent girls]. Ukrainskyi zhurnal dytiachoi endokrynolohii, 2, 83–84. [in Russian].

Budreyko, E.A., & Kosovcova, A.V. (2014). Polovye razlichiya dinamiki chuvstvitelnosti k insulinu u detej s ozhireniem na fone terapii metforminom [Sexual differences in the dynamics of insulin sensitivity in obese children with metformin therapy]. Ukrainskyi zhurnal dytiachoi endokrynolohii, 4, 13–17. [in Russian].

Kozlov, V. A. (2008). Metilirovanie DNK kletki i patologiya organizma [Methylation of cellular dna and pathology of the organism]. Medicinskaya immunologiya, 10(4–5), 307–318. [in Russian].

Kovaleva, O. A. (2008). Citologicheskie anomalii v somaticheskikh kletkakh mlekopitayushchikh [Cytological anomalies in somatic cells of mammals]. Citologiya i genetika, 42(1), 58–72. [in Russian].

Kovaleva, V. I., Budreyko, E. A., & Chumak, S. A. (2014). Immunocitogeneticheskaya kharakteristika detej, stradayushhikh sakharnym dіabetom I tipa [Immunocytogenetic characteristics in children with type I diabetes mellitus]. Faktory eksperymentalnoi evoliutsіi orhanіzmіv, (Vol. 14), (P. 204–207). Kyiv. [in Russian].

Boltіna, I. V. (2012). Chastota aberatsii khromomsom v kulturi limfotsytiv peryferychnoi krovi khvorykh na hliomy holovnoho mozku pry dii modelnykh mutaheniv mitomitsynu S ta dymetosteoartrozu (Avtoref. dis…kand. biol. nauk). [Frequency of aberaceous chromomas in cultures of lymphocytes in peripheral blood vessels on the glomi of the brain in the case of model mutagenes with mitomycin with dimethosteroarthrosis. (Extended abstract of candidate’s thesis). Kyiv. [in Ukrainian].

Bagatskaya, N. V. & Medzanovskaya, E. V. (2012). Osobennosti associirovaniya akrocentricheskikh khromosom u bol'nykh revmatoidnym artritom [Features of the association of acrocentric chromosomes in patients with rheumatoid arthritis]. Visnyk KhNU im. V.N. Karazina. Seriia: Biolohiia, 14(971), 71–76. [in Russian].

Bagatska, N. V., Kovaleva, V. I., Budreyko, Ye. A., & Chumak, S. A. (2015). Citogeneticheskaya kharakteristika detej, bol'nykh sakharnym diabetom I tipa, s uchetom primenyaemoj insulinoterapii [Cytogenetic characteristics of children with type 1 diabetes mellitus with consideration of the applied insulinotherapy]. Visnyk Kharkivskoho natsionalnoho universytetu imeni N.V. Karazina. Seriia: Biolohiia, 24(1153), 29–35. [in Russian].

Budreyko, O. A. (2013). Zastosuvannia analohіv іnsulіnu u dіtei ta pіdlіtkіv: problemnі pytannia ta mozhlyvostі dosiahnennia optymalnoi kompensatsii tsukrovoho dіabetu I typu [Use of insulin analogues in children and adolescents: topical issues and possibilities for achieving optimal type 1 diabetes mellitus compensation]. Mezhdunarodnyj e'ndokrinologichskij zhurnal, 2, 87–93. [in Ukrainian].

Budreyko, O. A. (2016). Udoskonalennia navchannia samokontroliu tsukrovoho dіabetu I typu u dіtei ta pіdlіtkіv [Improvement of self-control training of type 1 diabetes in children and adolescents]. Ukrainskyi zhurnal dytiachoi endokrynolohii, 1, 67–82. [in Ukrainian].

Grant, R. W., O'Brien, K. E., Waxler, J. L., et al. (2013) Personalizirovannoe geneticheskoe konsul'tirovanie o predraspolozhennosti k diabetu kak stimul k soblyudeniyu profilakticheskikh rekomendacij [Personalized genetic counseling about a predisposition to diabetes as an incentive to follow preventive recommendations]. Dіabet ozhyrіnnia metabolіchnyi sydrom, 1(II), 81–88. [in Russian].

Ruiter, R., Visser, L. E., van Herk-Sukel, M., Coebergh, P. P., Haak, J. W. W. H. R., Geelhoed-Duijvestijn, P. H., et al. (2012). Risk razvitiya onkozabolevanij u pacientov na insuline glargin i drugikh analogov insulina v sravnenii s pacientami na chelovecheskom insuline: rezultaty bol'shogo populyacionnogo katamnesticheskogo issledovaniya [The risk of cancer development in patients on insulin glargine and other insulin analogues in comparison with patients on human insulin: the results of a large population follow-up study]. Dіabet ozhyrіnnia metabolіchnyi sydrom, 1, 59–69. [in Russian].

Zerova-Lyubimova, T. E., & Horovenko, N. G. (2003). Standarty analіzu preparatіv khromosom liudyni [Standards for the analysis of human chromosomal preparations: methodical recommendations]. Kyiv [in Ukrainian].

Frolov, A. K., Arcimovich, N. G., & Sokhin, A. A. (1993). Immunocitogenetika [Immunocytogenetics]. Moskow: Medicina [in Russian].

Akopian, H. R. (2012). Tsytohenetychna nestabіlnіst ta polіmorfіzm khromosom v normі і pry patolohii liudyny (Avtoref. dis… dokt. med. nauk) [Cytogenetic instability and polymorphism of chromosomes in norm and at human pathology. Dr. med. sci. diss.]. Kyiv. [in Ukrainian].

Pilinskaya, M. A., Shemetun, A. M., Dybskij, S. S., & Red'ko, D. V. (1996). Geneticheskie e'ffekty v somaticheskikh kletkakh lic, rabotayushhikh v usloviyah khronicheskogo oblucheniya raznoj intensivnosti posle avarii na Chernobylskoj AE'S [Genetic effects in somatic cells of individuals working under conditions of chronic irradiation of different intensity after the Chernobyl accident]. Citologiya i genetika, 30(2), 17–21. [in Russian].

Akopian, H. R., Huleiuk, N. L., Kushnіruk, V. O., et al. (2013). Porivnialnyi analiz kariotypu novoi linii klityn liudyny 4VL v umovakh tryvaloho kultyvuvannia, ploidnist khromosomnoho naboru [Comparative analysis of the karyotype of a new line of human cells 4BL in conditions of prolonged cultivation, chromosome pallidity set]. Citologiya i genetika, 47, 55–69. [in Ukrainian].

Atramentova, L. A., & Utevskaya, O. M. (2008). Statisticheskie metody v biologii [Statistical methods in biology]. Gorlovka. [in Russian].

King, R. W. (2013). When 2 + 2 = 5: the origins and fates of aneuploid and tetraploid cels. Biochim. Biophys. Acta., 1786(1), 4–14. doi: 10.1016/j.bbcan.2008.07.007.

Mosieniak, G., & Sikora, E. (2010). Polyploidy: the link between senescence and cancer. Curr. Pharm. Des., 16(6), 734–740. doi: 10.2174/138161210790883714.

How to Cite

1.
Yeromenko RF, Kovalova VI, Lytvynova OM, Palamarchuk OO, Lytvynov VS. Determination of the chromosome aberrations frequency and the dynamics of acrocentric chromosomes associations in children with type I diabetes. Zaporozhye Medical Journal [Internet]. 2018Sep.24 [cited 2024Dec.26];(5). Available from: http://zmj.zsmu.edu.ua/article/view/141719

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Section

Basic research