Prevalence of myocilin gene mutations in a novel UK cohort of POAG patients

Ennis, Sarah; Gibson, Jane; Griffiths, Helen; Bunyan, David J.; Cree, Angela J.; Robinson, David; Self, James; MacLeod, Alex; Lotery, Andrew

doi:10.1038/eye.2009.73

Cited by 15 publications

(11 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…As of July 2011, 2072 participants have been recruited in the ANZRAG, the majority of which have advanced glaucoma ( n = 1214). In our advanced glaucoma cohort, 55.5% report a positive family history of glaucoma, which is higher than previous studies assessing a family history of glaucoma as self‐reported by participants with POAG among various populations (16–46% 8,9,27–34 ). Those studies usually considered a family history positive if first‐ or second‐degree relatives were affected with glaucoma, but half of them do not provide any specific details on their criteria.…”

Section: Discussioncontrasting

confidence: 66%

Australian and New Zealand Registry of Advanced Glaucoma: methodology and recruitment

Souzeau

Goldberg

Healey

et al. 2012

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

show abstract

Section: Discussioncontrasting

confidence: 66%

Australian and New Zealand Registry of Advanced Glaucoma: methodology and recruitment

Souzeau

Goldberg

Healey

et al. 2012

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

show abstract

“…The Myocilin protein is encoded by the MYOC gene and is expressed widely in the body, including in skeletal muscle, heart, lung, pancreas, corpus ciliare, trabecular meshwork, and retina [15]. Current international work holds the MYOC mutation rate to be approximately 2-6% in POAG patients [5,16]. The MYOC Y437H mutation is located in the third exon of MYOC and was first reported in 1998 [17].…”

Section: Discussionmentioning

confidence: 99%

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

Yang

Abdulatef

Zhang³

et al. 2020

Int. J. Med. Sci.

View full text Add to dashboard Cite

Objective: To identify the interaction between the MYOC Y437H mutation and TGF-β2 in a family with primary open-angle glaucoma (POAG). Methods: The MYOC Y437H mutation was identified in a family with POAG; the family was a fourth-generation family with 27 members, of which 6 members were affected. Analysis focused on the secreted myocilin protein and TGF-β2 found in the aqueous humor. Samples were taken both from normal controls and MYOC mutant carriers and cross-talk between MYOC Y437H and TGF-β2 were evaluated in the trabecular meshwork (TM) cells. Results: Aqueous humor secreted myocilin protein levels were reduced while TGF-β2 levels were increased in patients with the MYOC (c.1309T>C) mutation. This inverse relationship indicated that elevated TGF-β2 may be an important pathogenic mechanism in the progression of myocilin-related POAG. In TM cells expressing the MYOC Y437H mutant, exogenous TGF-β2 also significantly increased myocilin expression as well as the endoplasmic reticulum (ER) stress markers GRP94 and CHOP. This increase in TGF-β2 was also associated with increased cell death in cells carrying the MYOC Y437H mutation. Conclusion: These data collectively suggest that the mutual interaction between glaucomatous MYOC mutation and TGF-β2 contributed to the cell death of TM cells. This relationship also provides a new, therapeutic targets for the treatment of glaucoma.

show abstract

“…For the genetic analysis of IVAN samples, DNA was extracted and normalized from 10 ml of peripheral blood using an established method. 8 The SNP assays were performed using KASPar biochemistry as previously described. 5 …”

Section: Methodsmentioning

confidence: 99%

VEGFR2 Gene Polymorphisms and Response to Anti–Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration

et al. 2015

View full text Add to dashboard Cite

Purpose A previously published study demonstrated a pharmacogenetic association between the minor alleles of two VEGFR2 SNPs and greater improvement in visual acuity (VA) to treatment with ranibizumab, an anti-VEGF drug, in patients with neovascular age-related macular degeneration (nAMD). We evaluated whether this association was replicated among patients who participated in the Comparison of AMD Treatments Trials (CATT) or the Alternative Treatments to Inhibit VEGF in Patients with Age-Related Choroidal Neovascularisation (IVAN) trial. Design Cohort studies within randomized clinical trials. Participants 835 patients participating in CATT and 512 patients participating in IVAN. Methods Each patient was genotyped for SNPs rs4576072 and rs6828477 in the VEGFR2 gene. Main Outcomes Measures Mean change in VA from baseline one year after initiation of treatment with ranibizumab or bevacizumab. Differences in VA response between the patient group homozygous for the minor allele of each SNP and the other genotype groups were evaluated with analysis of variance. Differences in VA response by the number of minor alleles present for either SNP or both combined were evaluated with tests of linear trend. Analyses were conducted separately for CATT and IVAN participants and with both the studies combined. Results No statistically significant difference in mean change in VA was identified between genotypes of either SNP (p≥0.05). Furthermore, a stepwise analysis failed to show a significant interaction for either SNP based upon the number of minor alleles present. The lack of association was similar in both the CATT and IVAN cohorts and whether the analysis combined patients treated with either ranibizumab or bevacizumab or when restricted to patients treated with ranibizumab only. Conclusions The CATT and IVAN data do not support a pharmacogenetic association between the two VEGFR2 SNPs, rs4576072 and rs6828477, and change in VA response to anti-VEGF therapy in patients with nAMD.

show abstract

Prevalence of myocilin gene mutations in a novel UK cohort of POAG patients

Cited by 15 publications

References 11 publications

Australian and New Zealand Registry of Advanced Glaucoma: methodology and recruitment

Australian and New Zealand Registry of Advanced Glaucoma: methodology and recruitment

Cross-talk between MYOC p. Y437H mutation and TGF-β2 in the pathology of glaucoma

VEGFR2 Gene Polymorphisms and Response to Anti–Vascular Endothelial Growth Factor Therapy in Age-Related Macular Degeneration

Contact Info

Product

Resources

About