Genetic aspects of primary open-angle glaucoma in adults
Keywords:
Primary open-angle glaucoma, gene, Mendelian inheritance, blindnessAbstract
Glaucoma is the second leading cause of visual impairment and blindness worldwide. The main
type of glaucoma in many populations is the primary open-angle glaucoma (POAG); based
on the age of onset, a kind of early-onset POAG can be distiguished, called juvenile primary
open-angle glaucoma (JPOAG), which often shows a pattern of Mendelian inheritance. How-
ever, the most prevalent subtype is called adult-onset POAG, which in most cases displays a
complex pattern of inheritance. In general, more than 15 genetic loci have been reported, but
only five genes have been identified in these loci as a cause of glaucoma: myocilin (MYOC),
optineurin (OPTN), WD repeat domain 36 (WDR36), cytochrome P450 1B1 (CYP1B1) and
neurotrophin-4 (NTF4). However, the percentage of mutations in these genes in POAG pa-
tients is low; in some of these cases, a Mendelian inheritance pattern is observed, while in
a sizeable fraction of cases the phenotypes result from the contribution of a large number of
different variants of genes.
Publication Facts
Reviewer profiles N/A
Author statements
Indexed in
- Editor & editorial board
- profiles
- Academic society
- N/A
To learn about these publication facts, click 
PF is maintained by the Public Knowledge Project
References
Fan BJ, Wiggs JL. Glaucoma: genes, phenotypes, and
new directions for therapy. J Clin Invest. 2010; 120 (9):
-3072.
Quigley HA. Glaucoma. Lancet. 2011; 377: 1367-1377.
Fuse N. Genetic bases for glaucoma. Tohoku J Exp
Med. 2010; 221: 1-10.
Kwon YH, Fingert JH, Kuehn MH et al. Primary open-
angle glaucoma. N Engl J Med. 2009; 360 (11): 1113-
Ramakrishnan R, Khurana M. Surgical management of
glaucoma: an Indian perspective. Indian J Ophthalmol.
; 59 (Suppl): S118-122.
Rose R, Karthikeyan M, Anandan B et al. Myocilin mutation
among primary open angle glaucoma patients of Kanyaku-
mari district, South India. Mol Vis. 2007; 13: 497-503.
López-López G, Gastélum-Guerrero J. Prevalencia de
glaucoma primario en la coordinación universitaria del
Hospital Civil de Culiacán en el periodo 2003-2005. Bol
Med UAS. 2006; 12 (2): 12-15.
Gilbert-Lucido ME, García-Huerta M, Ruiz-Quintero N
et al. Estudio epidemiológico de glaucoma en población
mexicana. Rev Mex Oftalmol. 2010; 84 (2): 86-90.
Voleti VB, Hubschman JP. Age-related eye disease.
Maturitas. 2013; 75 (1): 29-33.
Klein R, Klein BE. The prevalence of age-related eye
diseases and visual impairment in aging: current esti-
mates. Invest Ophthalmol Vis Sci. 2013; 54 (14): 5-13.
Kini MM, Leibowitz HM, Colton T et al. Prevalence of
senile cataract, diabetic retinopathy, senile macular
degeneration, and open-angle glaucoma in the Fra-
mingham Eye Study. Am J Ophthalmol. 1978; 85: 28-34.
Goel M, Picciani RG, Lee RK et al. Aqueous humor
dynamics: a review. Open Ophthalmol J. 2010; 3 (4):
-59.
Sharts-Hopko NC, Glynn-Milley C. Primary open-angle
glaucoma. Am J Nurs. 2009; 109 (2): 40-47.
Wolfs RC, Klaver CC, Ramrattan RS et al. Genetic risk of
primary open-angle glaucoma. Arch Ophthalmol. 1998;
: 1640-1645.
Fan BJ, Wang DY, Lam DS et al. Gene mapping for
primary open angle glaucoma. Clin Biochem. 2006; 39
(3): 249-258.
Rao KN, Nagireddy S, Chakrabarti S. Complex gene-
tic mechanisms in glaucoma: an overview. Indian J
Ophthalmol. 2011; 59 (Suppl): S31-42.
Gadia R, Sihota R, Dada T et al. Current profi le of se-
condary glaucomas. Indian J Ophthalmol. 2008; 56 (4):
-289.
Khan AO. Genetics of primary glaucoma. Curr Opin
Ophthalmol. 2011; 22 (5): 347-355.
Challa P. Genetics of adult glaucoma. Int Ophthalmol
Clin. 2011; 51 (3): 37-51.
Allingham RR, Liu Y, Rhee DJ. The genetics of primary
open-angle glaucoma: a review. Exp Eye Res. 2009; 88:
-844.
Shields MB. Normal-tension glaucoma: is it different from
primary open-angle glaucoma? Curr Opin Ophthalmol.
; 19 (2): 85-88.
Soliman Mahdy MA. Gene therapy in glaucoma-part
I: Basic mechanisms and molecular genetics. Oman J
Ophthalmol. 2010; 3 (1): 2-6.
Challa P. Glaucoma genetics. Int Ophthalmol Clin. 2008;
(4): 73-94.
Ray K, Mookherjee S. Molecular complexity of primary
open angle glaucoma: current concepts. J Genet. 2009;
: 451-467.
Liu Y, Allingham RR. Molecular genetics in glaucoma.
Exp Eye Res. 2011; 93: 331-339.
Qu X, Zhou X, Zhou K et al. New mutation in the MYOC
gene and its association with primary open-angle
glaucoma in a Chinese family. Mol Biol Rep. 2010; 37:
-261.
Mengkegale M, Fuse N, Miyazawa A et al. Presence
of myocilin sequence variants in Japanese patients
with open-angle glaucoma. Mol Vis. 2008; 14: 413-
Xiao Z, Meng Q, Tsai JC et al. A novel optineurin genetic
mutation associated with open-angle glaucoma in a
chinese family. Mol Vis. 2009; 15: 1649-1654.
Miyazawa A, Fuse N, Mengkegale M et al. Association
between primary open-angle glaucoma and WDR36
DNA sequence variants in Japanese. Mol Vis. 2007;
: 1912-1919.
Burdon KP, Hewitt AW, Mackey DA et al. Tag SNPs
detect association of the CYP1B1 gene with primary
open angle glaucoma. Mol Vis. 2010; 16: 2286-2293.
Vithana EN, Nongpiur ME, Venkataraman D et al. Identi-
fi cation of a novel mutation in the NTF4 gene that causes
primary open-angle glaucoma in a Chinese population.
Mol Vis. 2010; 16: 1640-1645.
Chen LJ, Ng TK, Fan AH et al. Evaluation of NTF-4 as
a causative gene for primary open-angle glaucoma. Mol
Vis. 2012; 18: 1763-1772.
Ricard CS, Tamm ER. Focus on molecules: myocilin/
TIGR. Exp Eye Res. 2005; 81 (5): 501-502.
Tomarev SI, Nakaya N. Olfactomedin domain-containing
proteins: posible mechanisms of action and functions
in normal development and pathology. Mol Neurobiol.
; 40(2): 122-138.
Kanagavalli J, Pandaranayaka E, Krishnadas SR et al.
A review of genetic and structural understanding of the
role of myocilin in primary open angle glaucoma. Indian
J Ophthalmol. 2004; 52 (4): 271-280.
Xie X, Zhou X, Qu X et al. Two novel myocilin mutations
in a Chinese family with primary open-angle glaucoma.
Mol Vis. 2008; 14: 1666-1672.
Menaa F, Braghini CA, Vasconcellos JP et al. Keeping
an eye on myocilin: a complex molecule associated with
primary open-angle glaucoma susceptibility. Molecules.
; 16: 5402-5421.
López-Martínez F, López-Garrido MP, Sánchez-
Sánchez F et al. Role of MYOC and OPTN sequence
variations in Spanish patients with primary open-angle
glaucoma. Mol Vis. 2007; 13: 862-872.
Chalasani ML, Balasubramanian D, Swarup G. Focus on
molecules: optineurin. Exp Eye Res. 2008; 87 (1): 1-2.
Chalasani ML, Swarup G, Balasubramanian D. Opti-
neurin and its mutants: molecules associated with some
forms of glaucoma. Ophthalmic Res. 2009; 42: 176-184.
Park BC, Tibudan M, Samaraweera M et al. Interaction
between two glaucoma genes, optineurin and myocilin.
Genes Cells. 2007; 12 (8): 969-979.
Sripriya S, Nirmaladevi J, George R et al. OPTN gene:
profi le of patients with glaucoma from India. Mol Vis.
; 12: 816-820.
Fuse N, Takahashi K, Akiyama H et al. Molecular genetic
analysis of optineurin gene for primary open-angle and
normal tension glaucoma in the Japanese population.
J Glaucoma. 2004; 13: 299-303.
Chalasani ML, Balasubramanian D, Swarup G. Focus on
molecules: Optineurin. Exp Eye Res. 2008; 87 (1): 1-2.
Chalasani ML, Radha V, Gupta V et al. A glaucoma-as-
sociated mutant of optineurin selectively induces death
of retinal ganglion cells which is inhibited by antioxidants.
Invest Ophthalmol Vis Sci. 2007; 48: 1607-1614.
Sudhakar C, Nagabhushana A, Jain N et al. NF-kappaB
mediates tumor necrosis factor alpha-induced expres-
sion of optineurin, a negative regulator of NF-kappaB.
PLoS One. 2009; 4: e5114.
Hauser MA, Allingham RR, Linkroum K et al. Distribu-
tion of WDR36 DNAsequence variants in patients with
primary open-angle glaucoma. Invest Opthalmol Vis Sci.
; 47 (6): 2542-2546.
Fan BJ, Wang DY, Cheng CY et al. Different WDR36
mutation pattern IN Chinese patients with primary open-
angle glaucoma. Mol Vis. 2009; 15: 646-653.
Hewitt AW, Dimasi DP, Mackey DA et al. A glaucoma
case-control study of the WDR36 gen D658G sequence
variant. Am J Ophtalmol. 2006; 142 (2): 324-325.
Skarie JM, Link BA. The primary open-angle glaucoma
gene WDR36 functions in ribosomal RNA processing
and interacts with the p53 stress-response pathway.
Hum Mol Genet. 2008; 17: 2474-2485.
Messina-Baas OM, González-Huerta LM, Chima-Galán
C et al. Molecular analysis of the CYP1B1 gene: iden-
tifi cation of novel truncating mutations in patients with
primary congenital glaucoma. Ophthalmic Res. 2007;
(1): 17-23.
Stoilov I, Akarsu AN, Alozie I et al. Sequence analysis
and homology modeling suggest that primary congeni-
tal glaucoma on 2p21 results from mutation disrupting
either the hinge region or the conserved core structure
of cytochrome P450 1B1. Am J Hum Genet. 1998; 62
(3): 573-584.
Vincent AL, Billingsley G, Buys Y et al. Digenic inhe-
ritance of early-onset glaucoma: CYP1B1, a potential
modifi er gene. Am J Hum Genet. 2002; 70: 448-460.
Vasiliou V, Gonzalez FJ. Role of CYP1B1 in glaucoma.
Annu Rev Pharmacol Toxicol. 2008; 48: 333-350.
Ip NY, Ibañez CF, Nye SH et al. Mammalian neuro-
trophin-4: Structure, chromosomal localization, tissue
distribution, and receptor specifi city. Proc Natl Acad Sci
USA. 1992; 89 (7): 3060-3064.
Liu Y, Liu W, Crooks K et al. No evidence of associa-
tion of heterozygous NTF-4 mutations in patients with
primary open-angle glaucoma. Am J Hum Genet. 2010;
: 498-499.
Pasutto F, Matsumoto T, Mardin ChY et al. Hetero-
zygous NTF4 mutations impairing neurotrophin-4 sig-
naling in patients with primary open-angle glaucoma.
Am J Hum Genet. 2009; 85 (4): 447-456.
Rao KN, Kaur I, Parikh RS et al. Variations in NTF-4,
VAV2, and VAV3 genes are not involved with primary
open angle and primary angle closure glaucomas in an
Indian population. Invest Ophthalmol Vis Sci. 2010; 51
(10): 4937-4941.
Cheng L, Sapieha P, Kittlerova P et al. TrkB gene trans-
fer protects retinal ganglion cells from axotomy-induced
death in vivo. J Neurosci. 2002; 22: 3977-3986.
Berkemeier LR, Winslow JW, Kaplan DR et al. Neuro-
trophin-5: a novel neurotrophic factor that activates trk
and trkB. Neuron. 1991; 7: 857-866.
Burdon KP. Genome-wide association studies in the
hunt for genes causing primary open-angle glaucoma: a
review. Clin Experiment Ophthalmol. 2012; 40 (4): 358-
Thorleifsson G, Magnuson KP, Sulem P et al. Common
sequence variants in the LOXL1 gene confer suscep-
tibility to exfoliation glaucoma. Science. 2007; 317:
-1400.
Nakano M, Ikeda Y, Taniguchi T et al. Three susceptible
loci asociated with primary open-angle glaucoma identifi ed
by genome-wide association study in a Japanese popula-
tion. Proc Natl Acad Sci USA. 2009; 106: 12838-12842.
Fan BJ, Liu K, Wang DY et al. Association of polymor-
phisms of tumor necrosis factor and tumor protein p53
with primary open-angle glaucoma. Invest Ophthalmol
Vis Sci. 2010; 51: 4110-4116.
Wiggs JL, Kang JH, Yaspan BL et al. Common variants
near CAV1 and CAV2 are associated with primary open-
angle glaucoma in Caucasians from the USA. Hum Mol
Genet. 2011; 20 (23): 4707-4713.
Osman W, Low SK, Takahashi A et al. A genome-wide
association study in the Japanese population confi rms
p21 and 14q23 as susceptibility loci for primary open angle
glaucoma. Hum Mol Genet. 2012; 21 (12): 2836-2842.
Blue Mountains Eye Study (BMES), Wellcome Trust
Case Control Consortium 2 (WTCCC2). Genome-wide
association study of intraocular pressure identifi es the
GLCCI1/ICA1 region as a glaucoma susceptibility locus.
Hum Mol Genet. 2013; 22 (22): 4653-4660.
Nag A, Venturini C, Small KS et al. A genome-wide
association study of intra-ocular pressure suggests a
novel association in the gene FAM125B in the TwinsUK
cohort. Hum Mol Genet. 2014; 23 (12): 3343-3348.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra
This work is licensed under a Creative Commons Attribution 4.0 International License.
© Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra under a Creative Commons Attribution 4.0 International (CC BY 4.0) license which allows to reproduce and modify the content if appropiate recognition to the original source is given.
