Genetic epidemiology of hereditary predisposition to keratoconus
A. I. Solovev,
A. N. Kulicov,
S. V. Churashov,
D. V. Grigorev,
E. Y. Adoeva,
M. A. Levko,
V. Y. Kravtsov https://doi.org/10.34215/1609-1175-2021-3-11-16
Abstract
The survey of the literature devoted to genetic epidemiology of keratoconus and also principles of genetic markers search showed predisposition to this disease suitable for screening test in the course of genetic certification of the population. It was revealed that hereditary predisposition to keratokonus was caused by gene mutations, encoding cellular cycle and metabolism of the keratocytes regulating the activity of tissue proteolytic enzymes, and also mechanisms of natural detoxification. Genes associated with keratoconus are characterized by allelic variation and multiple mutations taking different degrees of association with clinically apparent diseases. It was discovered that genotypes of people from different geographic regions can differ in terms of signs and markers showing predisposition to the disease.
About the Authors
A. I. Solovev
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
MD, PhD, professor, Department of Biology,
6 Akademika Lebedeva St., Saint Petersburg, 194044
A. N. Kulicov
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
MD, PhD, associate professor, head of the Ophthalmology Department,
6 Akademika Lebedeva St., Saint Petersburg, 194044
S. V. Churashov
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
D. V. Grigorev
1477 Naval Clinical Hospital
Russian Federation
Russian Federation
MD, PhD, head of the Ophthalmology Department,
4 Ivanovskaya St., Vladivostok, 690005
E. Y. Adoeva
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
MD, PhD, associate professor,
6 Akademika Lebedeva St., Saint Petersburg, 194044
M. A. Levko
I.I. Mechnikov North-Western State Medical University
Russian Federation
Russian Federation
MD, PhD, associate professor, Ophthalmology Department,
41 Kirochnaya St., Saint Petersburg, 191015
V. Y. Kravtsov
S.M. Kirov Military Medical Academy
Russian Federation
Russian Federation
MD, PhD, professor, head of the Biology Department,
6 Akademika Lebedeva St., Saint Petersburg, 194044
References
1. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4):297–319.
2. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int. 2015. doi: 10.1155/2015/795738
3. Kulicov AN, Churashov SV, Kamilova TA, Reituzov VA. Molecular genetic aspects of keratoconus pathogenesis. Ophthalmology Journal. 2017;10(2):62–71(In Russ).
4. 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).
5. Abu-Amero KK, Al-Muammar AM, Kondkar AA. Genetics of keratoconus: Where do we stand? J Ophthalmol. 2014. doi:10.1155/2014/641708
6. Bae HA, Mills RAD, Lindsay RG, Phillips T, Coster DJ, Mitchell P, et al. Replication and meta-analysis of candidate loci identified variation at RAB3GAP1 associated with keratoconus. Invest Ophthalmol Vis Sci. 2013;54(7):5132–5.
7. Chang H-Y, Chodosh J. The genetics of keratoconus. Semin Ophthalmol. 2013;28(5–6):275–80.
8. Ali BM, Abdu M, Yaw CY, Mohidin N. Clinical characteristics of keratoconus patients in Malaysia: A review from a cornea specialist centre. J Optom. 2012;5(1):38–42.
9. Burdon KP, Macgregor S, Bykhovskaya Y, Javadiyan S, Li X, Laurie KJ, et al. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Invest Ophthalmol Vis Sci. 2011;52(11):8514–9.
10. Dudakova L, Palos M, Jirsova K, Stranecky V, Krepelova A, Hysi PG, Liskova P. Validation of rs2956540:G>C and rs3735520:G>A association with keratoconus in a population of European descent. Eur J Hum Genet. 2015;23(11):1581–3.
11. Liskova P, Dudakova L, Krepelova A, Klema J, Hysi PG. Replication of SNP associations with keratoconus in a Czech cohort. PLoS One. 2017; 12(2):e0172365. doi: 10.1371/journal.pone.0172365
12. Buddi R, Lin B, Atilano SR, Zorapapel NC, Kenney MC, Brown DJ. Evidence of oxidative stress in human corneal diseases. J Histochem Cytochem. 2002;50(3):341–51.
13. Gondhowiardjo TD, van Haeringen NJ, Völker-Dieben HJ, Beekhuis HW, Kok JHC, van Rij G, et al. Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas. Cornea. 1993;12(2):146–54.
14. Lema I, Durán JA. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmolog. 2005;112(4):654–9.
15. Lema I, Durán JA, Ruiz C, Díez-Feijoo E, Acera A, Merayo J. Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects. Cornea. 2008;27(7):758–63.
16. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004; 29(1):35–40.
17. Burdon KP, Vincent AL. Insights into keratoconus from a genetic perspective. Clin Exp Optom. 2013;96(2):146–54.
18. Héon E, Greenberg A, Kopp KK, Rootman D, Vincent AL, Billingsley G, et al. VSX1: A gene for posterior polymorphous dystrophy and keratoconus. Hum Mol Genet. 2002;11(9):1029–36.
19. Mazzotta C, Traversi C, Raiskup F, Rizzo CL, Renieri A. First identification of a triple corneal dystrophy association: Keratoconus, epithelial basement membrane corneal dystrophy and fuchs’ endothelial corneal dystrophy. Case Rep Ophthalmol. 2014;5(3):281–8.
20. Wheeler J, Hauser MA, Afshari NA, Allingham RR, Liu Y. The genetics of keratoconus: A review. Reprod Syst Sex Disord. 2012;S6:001. doi: 10.4172/2161-038X.S6-001
21. Li X, Bykhovskaya Y, Canedo AL, Haritunians T, Siscovick D, Aldave AJ, et al. Genetic association of COL5A1 variants in keratoconus patients suggests a complex connection between corneal thinning and keratoconus. Invest Ophthalmol Vis Sci. 2013;54(4):2696–704.
22. Sahebjada S, Schache M, Richardson AJ, Snibson G, Daniell M, Baird PN. Association of the hepatocyte growth factor gene with keratoconus in an Australian population. PLoS One. 2014;9(1):e84067. doi: 10.1371/journal.pone.0084067
23. Dudakova L, Liskova P, Trojek T, Palos M, Kalasova S, Jirsova K. Changes in lysyl oxidase (LOX) distribution and its decreased activity in keratoconus corneas. Exp Eye Res. 2012;104:74–81.
24. Zhang J, Zhang L, Hong J, Wu D, Xu J. Association of common variants in LOX with keratoconus: A meta-analysi. PLoS One. 2015;10(12):e0145815. doi: 10.1371/journal.pone.0145815
25. Atilano SR, Coskun P, Chwa M, Jordan N, Reddy V, Le K, et al. Accumulation of mitochondrial DNA damage in keratoconus corneas. Invest Ophthalmol Vis Sci. 2005;46(4):1256–63.
26. Chwa M, Atilano SR, Hertzog D, Zheng H, Langberg J, Kim DW, et al. Hypersensitive response to oxidative stress in keratoconus corneal fibroblasts. Invest Ophthalmol Vis Sci. 2008;49(10):4361–9.
27. Hsu R-J, Ho J-Y, Cha T-L, Yu D-S, Wu C-L, Huang W-P, et al. WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/β-catenin pathway. PLoS One. 2012;7(10):e47649. doi: 10.1371/journal.pone.0047649
28. Wojcik KA, Synowiec E, Sobierajczyk K, Izdebska J, Blasiak J, Szaflik J, Szaflik JP. Polymorphism of the DNA base excision repair genes in keratoconus. Int J Mol Sci. 2014;15(11):19682–99.
29. Baranov VS. Evolution of predictive medicine. Old ideas and new entities. Medical Genetics. 2017;16(5):4–9 (In Russ).
30. Okumura N, Minamiyama R, Ho L, Kay EP. Involvement of ZEB1 and Snail1 in excessive production of extracellular matrix in Fuchs endothelial corneal dystrophy. Lab Invest. 2015;95(11):1291–304.
31. Yellore VS, Rayner SA, Nguyen CK, Gangalum RK, Jing Z, Bhat SP, Aldave AJ. Analysis of the role of ZEB1 in the pathogenesis of posterior polymorphous corneal dystrophy. Invest Ophthalmol Vis Sci. 2012;53(1):273–8.
32. Goll DE, Thompson VF, Li H, Wei W, Cong J. The calpain system. Physiol Rev. 2003;83(3):731–801.
33. Mootha VV, Kanoff JM, Shankardas J, Dimitrijevich S. Marked reduction of alcohol dehydrogenase in keratoconus corneal fibroblasts. Mol Vis. 2009;15:706–12.
34. Nowak DM, Karolak JA, Kubiak J, Gut M. Substitution at IL1RN and deletion at SLC4A11 segregating with phenotype in familial keratoconus. Invest Ophthalmol Vis Sci. 2013;54(3):2207–15.
35. Sahebjada S, Schache M, Richardson AJ, Snibson G, MacGregor S, Daniell M, Baird PN. Evaluating the association between keratoconus and the corneal thickness genes in an independent Australian population. Invest Ophthalmol Vis Sci. 2013;54(13):8224–8.
36. Aldave AJ, Yellore VS, Salem AK, Yoo GL, Rayner SA, Yang H, et al. No VSX1 gene mutations associated with keratoconus. Invest Ophthalmol Vis Sci. 2006;47(7): 2820–2.
37. Dash DP, George S, O’Prey D, Burns D, Nabili S, Donnelly U, et al. Mutational screening of VSX1 in keratoconus patients from the European population. Eye. 2010;24(6):1085–92.
38. Loukovitis E, Sfakianakis K, Syrmakesi P, Tsotridou E, Orfanidou M, Bakaloudi DR, et al. Genetic aspects of keratoconus: A literature review exploring potential genetic contributions and possible genetic relationships with comorbidities. Ophthalmol Ther. 2018;7(2):263–92.
39. Pothula S, Bazan HE, Chandrasekher G. Regulation of Cdc42 expression and signaling is critical for promoting corneal epithelial wound healing. Invest Ophthalmol Vis Sci. 2013;54(8):5343–52.
40. Lechner J, Dash DP, Muszynska D, Hosseini M, Segev F, George S, et al. Mutational spectrum of the ZEB1 gene in corneal dystrophies supports a genotype-phenotype correlation. Invest Ophthalmol Vis Sci. 2013;54(5):3215–23.
41. Kokolakis NS, Gazouli M, Chatziralli IP, Koutsandrea C, Gadzioufas Z, Peponis VG, et al. Polymorphism analysis of COL4A3 and COL4A4 genes in Greek patients with keratoconus. Ophthalmic Genet. 2014;35(4):226–8.
42. Bykhovskaya Y, Li X, Epifantseva I, Haritunians T, Siscovick D, Aldave A, et al. Variation in the lysyl oxidase (LOX) gene is associated with keratoconus in family-based and case-control studies. Invest Ophthalmol Vis Sci. 2012;53(7):4152–7.
43. Hasanian-Langroudi F, Saravani R, Validad M-H, Bahari G, Yari D. Association of Lysyl oxidase (LOX) polymorphisms with the risk of keratoconus in an Iranian population. Ophthalmic Genet. 2015;36(4):309–14.
44. Synowiec E, Wojcik KA, Izdebska J, Binczyk E, Blasiak J, Szaflik J, Szaflik JP. Polymorphisms of the homologous recombination gene RAD51 in keratoconus and Fuchs endothelial corneal dystrophy. Dis Markers. 2013;35(5):353–62.
45. Jeyabalan N, Shetty R, Ghosh A, Anandula VR, Ghosh AS, Kumaramanickavel G. Genetic and genomic perspective to understand the molecular pathogenesis of keratoconus. Indian J Ophthalmol. 2013;61(8):384–8.
46. Li X, Bykhovskaya Y, Tang YG, Picornell Y, Haritunians T, Aldave A, et al. An association between the calpastatin (CAST) gene and keratoconus. Cornea. 2013;32(5):696–701.
47. Wójcik KA, Synowiec E, Jiménez-García MP, Kaminska A, Polakowski P, Blasiak J, et al. Polymorphism of the transferrin gene in eye diseases: keratoconus and Fuchs endothelial corneal dystrophy. Biomed Res Int. 2013. doi: 10.1155/2013/247438
48. Lu Y, Vitart V, Burdon KP, Khor CC, Bykhovskaya Y, Mirshahi A, et al. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nat Genet. 2013;45(2):155–63.
49. Abdulalieva FI. Epidemiology of keratoconus in different countries. The Russian Annals of Ophthalmology. 2018;134(1):104–6 (In Russ).
Review
For citations:
Solovev A.I., Kulicov A.N., Churashov S.V., Grigorev D.V., Adoeva E.Y., Levko M.A., Kravtsov V.Y. Genetic epidemiology of hereditary predisposition to keratoconus. Pacific Medical Journal. 2021;(3):11-16. (In Russ.) https://doi.org/10.34215/1609-1175-2021-3-11-16
Views:
384
Email this article 