Genetic polymorphisms of catalase (rs7943316), glutathione peroxidase-1 (rs1050450), and transferrin (rs8177178) in keratoconus on a limited group of Russian patients

Abstract

A pilot study of the association of single nucleotide polymorphisms in catalase (rs7943316), glutathione peroxidase-1 (rs1050450), and transferrin (rs8177178) genes with the risk of keratoconus development was conducted in a sample of Russian patients. Genotyping was performed by analyzing the polymorphism of the lengths of restriction fragments using a polymerase chain reaction. Venous blood samples from 25 patients with keratoconus treated at the Ophthalmology Clinic of the Kirov Military medical Academy in 2019 and 2020 were examined. The control group included 20 patients who had no clinical signs of keratoconus. The effect of the single nucleotide polymorphism rs7943316 of the catalase gene on the risk of keratoconus development has not been established. The T allele of the glutathione peroxidase-1 gene containing the rs1050450 polymorphism slightly increases the risk of keratoconus compared with the C allele (odds ratio = 1.91; 95% confidence interval = 0.75–4.85; p = 0.17). A moderate association of the A allele of the transferrin gene containing rs8177178 polymorphism with the occurrence of keratoconus and an increase in the incidence of the disease associated with the AG genotype was revealed (odds ratio = 5.67; 95% confidence interval = 1.07–30; p = 0.12). Thus, when examining a limited sample of Russian patients with keratoconus, it was not possible to identify a link between the disease and single nucleotide polymorphisms of catalase rs7943316 and glutathione peroxidase-1 rs1050450. The relationship between the polymorphism of the transferrin rs8177178 gene (allele A and genotype AG) and the risk of keratoconus development was weak and not significant. Thus, expanding the study sample and further studying the polymorphisms of the transferrin gene that affect the structure of the enzyme and reduce the effectiveness of antioxidant protection of the cornea were recommended.

Keywords

catalase / glutathione peroxidase-1 / transferrin / keratoconus / single nucleotide polymorphism / analysis of restriction fragment length polymorphism / genotyping / polymerase chain reaction / antioxidant protection

References

[1] Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297–319. DOI: 10.1016/s0039-6257(97)00119-7

[2] Rabinowitz Y.S. Keratoconus // Surv Ophthalmol. 1998. Vol. 42. No. 4. P. 297–319. DOI: 10.1016/s0039-6257(97)00119-7

[3] Bikbov MM, Usubov EL, Oganisyan KK, et al. Genetic aspects of keratoconus development. Russian Journal of Genetics. 2017;53(5):517–525. (In Russ.). DOI: 10.7868/S0016675817040026

[4] Бикбов М.М., Усубов Э.Л., Оганесян К.Х., и др. Роль генетических факторов в развитии кератоконуса // Генетика. 2017. Т. 53, № 5. С. 517–525. DOI: 10.7868/S0016675817040026

[5] Skorodumova LO, Belodedova AV, Sharova EI, Malyugin BE. Search for genetic markers for precise diagnostics of keratoconus. Biomeditsinskaya khimiya. 2019;65(1):9–20. (In Russ.). DOI: 10.7868/S0016675817040026

[6] Скородумова Л.О., Белодедова А.В., Шарова Е.И., Малюгин Б.Э. Поиск генетических маркеров для уточняющей диагностики кератоконуса // Биомедицинская химия. 2019. Т. 65, № 1. С. 9–20. DOI: 10.7868/S0016675817040026

[7] Abu-Amero KK, Al-Muammar AM, Kondkar AA. Genetics of keratoconus: where do we stand? J Ophthalmol. 2014;2014:641708. DOI: 10.1155/2014/641708

[8] Abu-Amero K.K., Al-Muammar A.M., Kondkar A.A. Genetics of keratoconus: where do we stand? // J Ophthalmol. 2014. Vol. 2014. ID 641708. DOI: 10.1155/2014/641708

[9] Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int. 2015;2015:795738. DOI: 10.1155/2015/795738

[10] Gordon-Shaag A., Millodot M., Shneor E., Liu Y. The genetic and environmental factors for keratoconus // Biomed Res Int. 2015. Vol. 2015. ID 795738. DOI: 10.1155/2015/795738

[11] Chang H-Y, Chodosh J. The genetics of keratoconus. Semin Ophthalmol. 2013;28(5-6):275–280. DOI: 10.3109/08820538.2013.825295

[12] Chang H.-Y., Chodosh J. The genetics of keratoconus // Semin Ophthalmol. 2013. Vol. 28. No. 5-6. P. 275–280. DOI: 10.3109/08820538.2013.825295

[13] Solovev AI, Kulicov AN, Churashov SV, et al. Genetic epidemiology of hereditary predisposition to keratoconus. Pacific Medical Journal. 2021;(3):11–16. (In Russ.). DOI: 10.34215/1609-1175-2021-3-11-16

[14] Соловьев А.И., Куликов А.Н., Чурашов С.В., и др. Генетическая эпидемиология наследственной предрасположенности к кератоконусу // Тихоокеанский медицинский журнал. 2021. № 3. С. 11–16. DOI: 10.34215/1609-1175-2021-3-11-16

[15] Kirkman HN, Gaetani GF. Catalase: a tetrameric enzyme with four tightly bound molecules of NADPH. Proc Natl Acad Sci USA. 1984;81(14):4343–4347. DOI: 10.1073/pnas.81.14.4343

[16] Kirkman H.N., Gaetani G.F. Catalase: a tetrameric enzyme with four tightly bound molecules of NADPH // Proc Natl Acad Sci USA. 1984. Vol. 81. No. 14. P. 4343–4347. DOI: 10.1073/pnas.81.14.4343

[17] Sabet EE, Salehi Z, Khodayari S, et al. Polymorphisms of glutathione peroxidase 1 (GPX1 Pro198Leu) and catalase (CAT C-262T) in women with spontaneous abortion. Syst Biol Reprod Med. 2014;60(5):304–307. DOI: 10.3109/19396368.2014.892651

[18] Sabet E.E., Salehi Z., Khodayari S., et al. Polymorphisms of glutathione peroxidase 1 (GPX1 Pro198Leu) and catalase (CAT C-262T) in women with spontaneous abortion // Syst Biol Reprod Med. 2014. Vol. 60. No. 5. P. 304–307. DOI: 10.3109/19396368.2014.892651

[19] Vitai M, Fátrai S, Rass P, et al. Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus. Clin Chem Lab Med. 2005;43(12):1346–1350. DOI: 10.1515/CCLM.2005.230

[20] Vitai M., Fátrai S., Rass P., et al. Simple PCR heteroduplex, SSCP mutation screening methods for the detection of novel catalase mutations in Hungarian patients with type 2 diabetes mellitus // Clin Chem Lab Med. 2005. Vol. 43. No. 12. P. 1346–1350. DOI: 10.1515/CCLM.2005.230

[21] Flekac M, Skrha J, Hilgertova J, et al. Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus. BMC Med Genet. 2008;2008(9):30. DOI: 10.1186/1471-2350-9-30

[22] Flekac M., Skrha J., Hilgertova J., et al. Gene polymorphisms of superoxide dismutases and catalase in diabetes mellitus // BMC Med Genet. 2008. Vol. 2008. No. 9. ID 30. DOI: 10.1186/1471-2350-9-30

[23] Crawford A, Fassett RG, Geraghty DP, et al. Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease. Gene. 2012;501(2):89–103. DOI: 10.1016/j.gene.2012.04.011

[24] Crawford A., Fassett R.G., Geraghty D.P., et al. Relationships between single nucleotide polymorphisms of antioxidant enzymes and disease // Gene. 2012. Vol. 501. No. 2. P. 89–103. DOI: 10.1016/j.gene.2012.04.011

[25] Nemoto M, Nishimura R, Sasaki T, et al. Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography. Cardiovasc Diabetol. 2007;2007(6):23. DOI: 10.1186/1475-2840-6-23

[26] Nemoto M., Nishimura R., Sasaki T., et al. Genetic association of glutathione peroxidase-1 with coronary artery calcification in type 2 diabetes: a case control study with multi-slice computed tomography // Cardiovasc Diabetol. 2007. Vol. 2007. No. 6. ID 23. DOI: 10.1186/1475-2840-6-23

[27] Yang F, Lum JB, McGill JR, et al. Human transferrin: cDNA characterization and chromosomal localization. Proc Natl Acad Sci USA. 1984;81(9):2752–2756. DOI: 10.1073/pnas.81.9.2752

[28] Yang F., Lum J.B., McGill J.R., et al. Human transferrin: cDNA characterization and chromosomal localization // Proc Natl Acad Sci USA. 1984. Vol. 81. No. 9. P. 2752–2756. DOI: 10.1073/pnas.81.9.2752

[29] Yari D, Saravani R, Saravani S, et al. Genetic Polymorphisms of Catalase and Glutathione Peroxidase-1 in Keratoconus. Iran J Public Health. 2018;47(10):1567–1574. PMID: 30524988.

[30] Yari D., Saravani R., Saravani S., et al. Genetic Polymorphisms of Catalase and Glutathione Peroxidase-1 in Keratoconus // Iran J Public Health. 2018. Vol. 47. No. 10. P. 1567–1574. PMID: 30524988.

[31] Rickham PP. Human experimentation. Code of ethics of the world medical association. Declaration of Helsinki. Br Med J. 1964;5402(2):177. DOI: 10.1136/bmj.2.5402.177

[32] Rickham P.P. Human experimentation. Code of ethics of the world medical association. Declaration of Helsinki // Br Med J. 1964. Vol. 5402. No. 2. P. 177. DOI: 10.1136/bmj.2.5402.177

[33] Kimmelman J, Weijer C, Meslin EM. Helsinki discords: FDA, ethics, and international drug trials. The Lancet. 2009;373(9657):13–14. DOI: 10.1016/s0140-6736(08)61936-4

[34] Kimmelman J., Weijer C., Meslin E.M. Helsinki discords: FDA, ethics, and international drug trials // The Lancet. 2009. Vol. 373. No. 9657. P. 13–14. DOI: 10.1016/s0140-6736(08)61936-4

[35] Saravani R, Hasanian-Langroudi F, Validad MH, et al. Evaluation of possible relationship between COL4A4 gene polymorphisms and risk of keratoconus. Cornea. 2015;34(3):318–322. DOI: 10.1097/ICO.0000000000000356

[36] Saravani R., Hasanian-Langroudi F., Validad M.H., et al. Evaluation of possible relationship between COL4A4 gene polymorphisms and risk of keratoconus // Cornea. 2015. Vol. 34. No. 3. P. 318–322. DOI: 10.1097/ICO.0000000000000356

[37] Baudouin C, Brignole F, Fredj-Reygrobellet D, et al. Transferrin receptor expression by retinal pigment epithelial cells in proliferative vitreoretinopathy. Invest Ophthalmol Vis Sci. 1992;33(10):2822–2829. PMID: 1382045

[38] Baudouin C., Brignole F., Fredj-Reygrobellet D., et al. Transferrin receptor expression by retinal pigment epithelial cells in proliferative vitreoretinopathy // Invest Ophthalmol Vis Sci. 1992. Vol. 33. No. 10. P. 2822–2829. PMID: 1382045

[39] Wójcik KA, Synowiec E, Jiménez-García MP, et al. Polymorphism of the transferrin gene in eye diseases: keratoconus and Fuchs endothelial corneal dystrophy. Biomed Res Int. 2013;2013:247438. DOI: 10.1155/2013/247438

[40] Wójcik K.A., Synowiec E., Jiménez-García M.P., et al. Polymorphism of the transferrin gene in eye diseases: keratoconus and Fuchs endothelial corneal dystrophy // Biomed Res Int. 2013. Vol. 2013. ID 247438. DOI: 10.1155/2013/247438

RIGHTS & PERMISSIONS

Solovev A.I., Churashov S.V., Kulikov A.N., Buleev A.V., Krutikova A.A., Arukov A.R., Kravtsov V.Y.