ASSOCIATION OF DELETED POLYMORPHISM OF THE GLUTATHION-S-TRANSFERASE GENE WITH PRIMARY OPEN-GLASS GLAUCOMA
Keywords:primary open-angle glaucoma, polymorphism of the glutathione-S-transferase gene (GSTM1 i GSTT1)
Aim: to determine the association of deletion polymorphisms of the GST gene (GSTM1 and GSTT1) with the development of primary open angle glaucoma (POAG) in patients from the Ukrainian population.
Materials and methods. 172 patients with POAG of stages I–IV were examined in the Kyiv City Clinical Ophthalmological Hospital “Eye Microsurgery Center” – the clinical base of the Department of Ophthalmology of the National Medical Academy of Postgraduate Education. Analysis of the deletion polymorphism of the GSTM1 and GSTT1 genes was carried out by real-time polymerase chain reaction using the unifi ed test systems of TaqMan Mutation Detection Assays Life-Technology (USA). Statistical analysis of the obtained data was carried out using the MedStat package and the MedCalc v.15.1 statistical package (MedCalc Software bvba).
Results and discussion. The detection of “zero” alleles of the GSTM1 gene was noted in 39 % of patients in the control group, in patients with POAG, a signifi cant increase in the frequency of deletion polymorphism up to 50–56 % was observed with the progression of the disease to stage II–IV. In patients with stage IV, the infl uence of the GSTM1-null allele on the course of POAG (χ2=3.97, p=0.047) was determined, and the zero GSTM1 allele doubled the likeli hood of the disease (OR=2.01; 95 % CI=1.01–4.01) in patients of the 4th group in comparison with the control. The “zero” allele of the GSTT1 gene in the control group was detected in 31 %, the increase in the GSTT1-null allele frequency was also noted in II–IV stages of the POAG: from 41 % to 54 %. The statistically signifi cant differences in the frequencies of alleles of the GSTT1 gene between the control group and all patients with POAG (χ2=4.43, p=0.03), between the control group and the 4th group (χ2=7.64, p=0.01) and between the 1-st and 4-th groups (χ2=5.52, p=0.02).
For the deletion polymorphism of the GSTT1 gene, association with the development of POAG (χ2=4.43, p=0.03) was determined when comparing the control group with the data of all patients with POAG (1–4 groups). When stratifi cation by stages of POAG (i.e., by groups of patients), association with the development of POAG was determined only for patients of the 4th group (χ2=7.64, p=0.01) in comparison with the control group.
Conclusions. As a result of the study, the association of the “zero” allele of the GSTT1 gene with POAG (p=0.03) was established. The presence of the allele GSTT1-null signifi cantly increased the risk of developing POAG (OR=1.75, CI=1.04–2.96) compared with the control group. The presence of “null” alleles (GSTM1-null and GSTT1-null) of deletion polymorphism of the GST gene increased the risk of development of stage IV of POAG (OR=2.01; CI=1.01–4.01 and OR=2.66; CI=1,32–5,37, respectively) compared with the control group, which indicated the effect of “zero” alleles on the rate of progression of the disease.
Авдеев Р. В. Модель первичной открытоугольной глаукомы: манифестирование и исходы / Р. В. Авдеев, А. С. Александров, Н. А Бакунина [и др.] // Клиническая медицина. – 2014. – № 12. – С. 64–72.
Еричев В. П. О патогенезе первичной открытоугольной глаукомы / В. П. Еричев, Е. А. Егоров // Вестник офтальмологии. – 2014. – № 6. – С. 98–104.
Кириленко М. Ю. Генетические исследования первичной открытоугольной глаукомы / М. Ю. Кириленко, М. И. Чурносов // Вестник ТГУ. – 2014. – Т. 19, № 4. – С. 1140–1142.
Нестеров А. П. Глаукома / А. П. Нестеров. – М.: ООО «Медицинское информационное агентство», 2008. – 360 с.
Реброва О. Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ STATISTICA / О. Ю. Реброва. – М.: Медиа Сфера, 2002. – 312 с.
Сердюк В. М. Клініко-експериментальне обґрунтування нейропротекції в комплексі лікування хворих на первинну відкритокутову глаукому: дис. … д-ра мед. н. 14.01.18 «Офтальмологія» /В. М. Сердюк – Донецьк, 2014. – 314 с.
Тикунова Е. В. Молекулярные основы этиопатогенеза первичной открытоугольной глаукомы / Е. В. Тикунова // Научные ведомости. Серия Медицина. Фармация. – 2013. – Выпуск 22, № 11 (154). – С. 161–165.
Шепелюк Г. Г. Індивідуальний підхід у підборі місцевих гіпотензивних засобів для лікування первинної відкритокутової глаукоми / Г. Г. Шепелюк, Г. С. Шепелюк // Вісник ВДНЗУ «Українська медична стоматологічна академія». – 2010. – Т. 10, № 2. – С. 121–123.
Hayes K. R. Expression quantitative trait loci mapping identifi es new genetic models of glutathione S-transferase variation. / K. R. Hayes, B. M. Young, M. T. Pletcher // Drug Metab Dispos. – 2009. – Vol. 37. – P. 1269–1276.
Josephy P. D. Genetic variations in human glutathione transferase enzymes: signifi cance for pharmacology and toxicology / P. D. Josephy // Hum. Genomics Proteomics. – 2010. – e 876940.
Kapetanakis V. V. Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis //V. V. Kapetanakis, M. P. Y. Chan, P. J. Foster [et al.] // Br. J. Ophthalmol. –2016. – Vol. 100. – P. 86–93.
Rocha A. V. Is the GSTM1-null polymorphism a risk factor in primary open angle glaucoma? / A. V. Rocha, T. Talbot, T. Magalhaes da Silva [et al.] // Mol. Vis. – 2011. – Vol. 17. – P. 1679–1686.
Senthilkumar P. GST M1-T1 null Allele Frequency Patterns in Geographically Assorted Human Populations: A Phylogenetic Approach / P. Senthilkumar, R. Thirumurugan, A. Jayachitra [et al.] // PLoS One. – 2015. – № 10. – e 0118660.
Yildirim O. May glutathione S-transferase M1 positive genotype afford protection against primary open-angle glaucoma? / O. Yildirim, N. A. Ates, L. Tamer [et al.] // Graefes Arch. Clin, Exp. Ophthalmol. – 2005. – Vol. 243. – P. 327–333.
Yu Y. Association of Glutathione S transferases Polymorphisms with Glaucoma: A Meta-Analysis / Y. Yu, Y. Weng, J. Guo [et al.] // PloS One. – 2013. – Vol. 8 (1). – e 54037.
Copyright (c) 2019 Archive of Ukrainian Ophthalmology
This work is licensed under a Creative Commons Attribution 4.0 International License.
Our edition uses the copyright terms of Creative Commons for open access journals.
Authors, who are published in this journal, agree with the following terms:
- The authors retain rights for authorship of their article and grant to the edition the right of first publication of the article on a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published article, with the obligatory reference to the authors of original works and original publication in this journal.
- Directing the article for the publication to the editorial board (publisher), the author agrees with transmitting of rights for the protection and using the article, including parts of the article, which are protected by the copyrights, such as the author’s photo, pictures, charts, tables, etc., including the reproduction in the media and the Internet; for distributing; for the translation of the manuscript in all languages; for export and import of the publications copies of the writers’ article to spread, bringing to the general information.
- The rights mentioned above authors transfer to the edition (publisher) for the unlimited period of validity and on the territory of all countries of the world.
- The authors guarantee that they have exclusive rights for using of the article, which they have sent to the edition (publisher). The edition (the publisher) is not responsible for the violation of given guarantees by the authors to the third parties.
- The authors have the right to conclude separate supplement agreements that relate to non-exclusive distribution of their article in the form in which it had been published in the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.
- The policy of the journal permits and encourages the publication of the article in the Internet (in institutional repository or on a personal website) by the authors, because it contributes to productive scientific discussion and a positive effect on efficiency and dynamics of the citation of the article.
- The rights to the article are deemed transferred by the authors to the edition (the publisher) since the moment of the publication of the article in the printed or electronic version of journal.