Journal of Current Glaucoma Practice

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VOLUME 9 , ISSUE 3 ( September-December, 2015 ) > List of Articles


CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma

Muneeb A Faiq, Rizwana Qadri

Keywords : CYP1B1 gene, Functional genomics, Glaucoma, Intraocular pressure, Pathobiology, Primary congenital glaucoma, Trabecular meshwork

Citation Information : Faiq MA, Qadri R. CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015; 9 (3):77-80.

DOI: 10.5005/jp-journals-10008-1189

License: CC BY-NC 4.0

Published Online: 01-08-2019

Copyright Statement:  Copyright © 2015; The Author(s).


CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene.

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  1. Bofinger DP, Feng L, Chi LH, Love J, Stephen FD, Sutter TR, Osteen K, Costich GTG, Batt RE, Koury ST, et al. Effect of TCDD exposure on CYP1A1 and CYP1B1 expression in explant cultures of human endometrium. Toxicol Sci 2001 Aug;62(2):299-314.
  2. Hakkola J, Pasanen M, Pelkonen O, Hukkanen J, Evisalmi S, Anttila S, Rane A, Mäntylä M, Purkunen R, Saarikoski S, et al. Expression of CYP1B1 in human adult and fetal tissues and differential inducibility of CYP1B1 and CYP1A1 by Ah receptor ligands in human placenta and cultured cells. Carcinogenesis 1997 Feb;18(2):391-397.
  3. Stoilov I, Akarsu AN, Sarfarazi M. Identification of three different truncating mutations in cytochrome P4501B1 (CYP1B1) as the principal cause of primary congenital glaucoma (Buphthalmos) in families linked to the GLC3A locus on chromosome 2p21. Hum Mol Genet 1997;6(4):641-647.
  4. Bejjani BA, Lewis RA, Tomey KF, Anderson KL, Dueker DK, Jabak M, Astle WF, Otterud B, Leppert M, Lupski JR. Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudia Arabia. Am J Hum Genet 1998 Feb;62(2):325-333.
  5. Buters JT, Doehmer J, Gonzalez FJ. Cytochrome P450-null mice. Drug Metab Rev 1999 May;31(2):437-447.
  6. Vasiliou VI, Gonzalez FJ. Role of CYP1B1 in glaucoma. Annu Rev Pharmacol Toxicol 2008;48(1):333-358.
  7. Bailey LR, Roodi N, Dupont WD, Parl FF. Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid hormone receptor status in breast cancer. Cancer Res 1998 Nov; 58(22):5038-5041.
  8. Li DN, Seidel A, Pritchard MP, Wolf CR, Friedberg T. Polymorphisms in P450 CYP1B1 affect the conversion of estradiol to the potentially carcinogenic metabolite 4-hydroxyestradiol. Pharmacogenetics 2000 Jun;10(4):343-353.
  9. deLuise VP, Anderson DR. Primary infantile glaucoma (congenital glaucoma). Surv Ophthalmol 1983 Jul-Aug;28(1):1-19.
  10. Gencik A, Gencikova A, Ferak V. Population genetical aspects of primary congenital glaucoma. I. Incidence, prevalence, gene frequency, and age of onset. Hum Genet 1982;61(3): 193-197.
  11. Sarfarazi M, Akarsu AN, Hossain A, Turacli ME, Aktan SG, Barsoum-Homsy M, Chevrette L, Sayli BS. Assignment of a locus (GLC3A) for primary congenital glaucoma (Buphthalmos) to 2p21 and evidence for genetic heterogeneity. Genomics 1995 Nov;30(2):171-177.
  12. Akarsu AN, Turacli ME, Aktan SG, Barsoum-Homsy ML, Chevrette B, Sayli S, Sarfarazi M. A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region. Hum Mol Genet 1996 Aug;5(8):1199-1203.
  13. Stoilov IR, Sarfarazi M. The third genetic locus (GLC3C) for primary congenital glaucoma (PCG) maps to chromosome 14q24.3. Invest Ophthalmol Vis Sci 2002 Dec;43(13):3015.
  14. Stoilov I. Cytochrome P450s: coupling development and environment. Trends Genet 2001 Nov;17(11):629-632.
  15. Stoilov I, Jansson I, Sarfarazi M, Schenkman JB. Roles of cytochrome p450 in development. Drug Metabol Drug Interact 2001;18(1):33-55.
  16. Doshi M, Marcus C, Bejjani BA, Edward DP. Immunolocalization of CYP1B1 in normal, human, fetal and adult eyes. Exp Eye Res 2006 Jan;82(1):24-32.
  17. Li N, Zhou Y, Du L, Wei M, Chen X. Overview of Cytochrome P450 1B1 gene mutations in patients with primary congenital glaucoma. Exp Eye Res 2011 Nov;93(5):572-579.
  18. Faiq MA, Sharma R, Dada R, Mohanty K, Saluja D, Dada T. Genetic, biochemical and clinical insights into primary congenital glaucoma. J Curr Glaucoma Prac 2013 May- Aug;7(2):66-84.
  19. Plasilova M, Gerinec A, Ferak V, Molecular diagnosis of mutations responsible for recurrent and severe forms of primary congenital glaucoma. Cesk Slov Oftalmol 1998;54(5): 281-288.
  20. Plasilova M, Ferakova E, Kadasi L, Polakova H, Gerinec A, Ott J, Ferak V. Linkage of autosomal recessive primary congenital glaucoma to the GLC3A locus in Roms (Gypsies) from Slovakia. Hum Hered 1998 Jan-Feb;48(1):30-33.
  21. Stoilov I, Akarsu AN, Alozie I, Child A, Barsoum-Homsy M, Tyracli MA, Or M, Lewis RA, Ozdemir N, Brice GA, et al. Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1. Am J Hum Genet 1998 Mar;62(3):573-584.
  22. Kakiuchi T, Isashiki Y, Nakao K, Sonoda S, Kimura K, Ohba N. A novel truncating mutation of cytochrome P4501B1 (CYP1B1) gene in primary infantile glaucoma. Am J Ophthalmol 1999 Sep;128(3):370-372.
  23. Bejjani BA, Stockton DW, Lewis RA, Tomey KF, Dueker DK, Jabak M, Astle WF, Lupski JR. Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus. Hum Mol Genet 2000 Feb;9(3):367-374.
  24. Martin SN, Sutherland J, Levin AV, Klose R, Priston M, Heon E. Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness. J Med Genet 2000 Jun;37(6):422-427.
  25. Ohtake Y, Kubota R, Tanino T, Miyata H, Mashima Y. Novel compound heterozygous mutations in the cytochrome P4501B1 gene (CYP1B1) in a Japanese patient with primary congenital glaucoma. Ophthalmic Genet 2000 Sep;21(3): 191-193.
  26. Mashima Y, Suzuki Y, Sergeev Y, Ohtake Y, Tanino T, Kimura I, Miyata H, Aihara M, Tanihara H, Inatani M, et al. Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma. Invest Ophthalmol Vis Sci 2001 Sep;42(10):2211-2216.
  27. Stoilov IR, Costa VP, Vasconcellos JP, Melo MB, Betinjane AJ, Carani JC, Oltrogge EV, Sarfarazi M. Molecular genetics of primary congenital glaucoma in Brazil. Invest Ophthalmol Vis Sci 2002 Jun;43(6):1820-1827.
  28. Panicker SG, Reddy AB, Mandal AK, Ahmed N, Nagarajaram HA, Hasnain SE, Balasubramanian D. Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees. Invest Ophthalmol Vis Sci 2002 May;43(5):1358-1366.
  29. Reddy AB, Kaur K, Mandal AK, Panicker SG, Thomas R, Hasnain SE, Balasubramanian D, Chakrabarti S. Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients. Mol Vis 2004 Sep;10:696-702.
  30. Tanwar M, Dada T, Sihota R, Dada R. Identification of four novel cytochrome P4501B1 mutations (p.I94X, p.H279D, p.Q340H, and p.K433K) in primary congenital glaucoma patients. Mol Vis 2009 Dec;15:2926-2937.
  31. Tanwar M, Dada T, Sihota R, Das TK, Yadav U, Dada R. Mutation spectrum of CYP1B1 in north Indian congenital glaucoma patients. Mol Vis 2009 Jun;15:1200-1209.
  32. Faiq MA, Dada R, Sharma R, Saluja D, Dada T. CYP1B1: A unique gene with unique characteristics. Curr Drug Metab 2014;15(9):893-914.
  33. Faiq MA, Ali M, Dada T, Dada R, Saluja D. A novel methodology for enhanced and consistent heterologous expression of unmodified human cytochrome P450 1B1 (CYP1B1). PLoS One 2014 Oct 16;9(10):e110473.
  34. Choudhary D, Jansson I, Sarfarazi M, Schenkman JB. Characterization of the biochemical and structural phenotypes of four CYP1B1 mutations observed in individuals with primary congenital glaucoma. Pharmacogenet Genomics 2008 Aug;18(8):665-676.
  35. Nagarajaram HA, Reddy BV, Blundell TL. Analysis and prediction of inter-strand packing distances between betasheets of globular proteins. Protein Eng 1999 Dec;12(12): 1055-1062.
  36. Reddy BV, Blundell TL. Packing of secondary structural elements in proteins. Analysis and prediction of inter-helix distances. J Mol Biol 1993 Oct;233(3):464-479.
  37. Reddy BV, Nagarajaram HA, Blundell TL. Analysis of interactive packing of secondary structural elements in alpha/beta units in proteins. Protein Sci 1999 Mar;8(3): 573-586.
  38. Sunyaev S, Ramensky V, Koch I, Lathe W, Kondrashov AS, Bork P. Prediction of deleterious human alleles. Hum Mol Genet 2001 Mar;10(6):591-597.
  39. Wang Z, Moult J. SNPs, protein structure, and disease. Hum Mutat 2001 Apr;17(4):263-270.
  40. Panicker SG, Mandal AK, Reddy AB, Gothwal VK, Hasnain SE. Correlation of genotype with phenotype in Indian patients with primary congenital glaucoma. Invest Ophthalmol Vis Sci 2004 Apr;45(4):1149-1156.
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