Dataset Information

No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients.

ABSTRACT:

Purpose

Substantial evidence suggests that ocular perfusion is regulated by nitric oxide (NO), and polymorphisms in genes encoding for enzymes involved in NO formation and degradation (endothelial nitric oxide synthase [NOS3] and cytochrome b-235 alpha polypeptide gene [CYBA]) might contribute to vascular dysregulation observed in glaucoma. We therefore assessed the association of glaucoma with polymorphisms of NOS3 and CYBA previously associated with cardiovascular disease. We also compared the distribution of these polymorphisms in patients with high tension glaucoma (HTG) and normal tension glaucoma (NTG) and evaluated its association with vascular dysregulation in a subset of glaucoma patients.

Methods

Three hundred Caucasian patients with HTG and 127 with NTG were enrolled in the study and genotyped for G894T (rs1799983) and T-786C (rs2070744) in NOS3 and C242T (rs4673) in CYBA.

Results

None of these polymorphisms had a different allele or genotype distribution between HTG and NTG patients nor had the presence of vasospasms any impact.

Conclusions

We studied the frequencies of a set of relevant polymorphisms of the NO system in a large cohort of glaucoma patients and found no association. These results therefore suggest the absence of a relevant relationship with different glaucoma forms in Caucasians.

SUBMITTER: Weiss J

PROVIDER: S-EPMC3425578 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients.

Weiss Johanna J Fränkl Stephan A SA Flammer Josef J Grieshaber Matthias C MC Hollo Gabor G Teuchner Barbara B Haefeli Walter Emil WE

Molecular vision 20120807

<h4>Purpose</h4>Substantial evidence suggests that ocular perfusion is regulated by nitric oxide (NO), and polymorphisms in genes encoding for enzymes involved in NO formation and degradation (endothelial nitric oxide synthase [NOS3] and cytochrome b-235 alpha polypeptide gene [CYBA]) might contribute to vascular dysregulation observed in glaucoma. We therefore assessed the association of glaucoma with polymorphisms of NOS3 and CYBA previously associated with cardiovascular disease. We also comp ...[more]

PMID: 22919264

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Project description:AIM:Polymorphisms in OPA1, the gene responsible for autosomal dominant optic atrophy, were recently found to be strongly associated with normal tension glaucoma (NTG). The aim of this study was to determine whether OPA1 polymorphisms affect the phenotype of NTG patients. METHODS:A retrospective analysis was performed of 108 well characterised NTG patients who had been genotyped for OPA1 variations, and who had previously undergone automated perimetry and Heidelberg retina tomography (HRT). 25 NTG patients had the at-risk OPA1 genotype (IVS 8 +4 C/T; +32 T/C) and 83 NTG patients did not. Differences between groups were sought in a wide range of structural, psychophysical, and demographic factors. These included sex, age at diagnosis, family history of glaucoma, history of ischaemic risk factors and vasospasm, laterality of glaucoma, presenting and highest diurnal intraocular pressure (IOP), initial cup-disc (CD) ratio, baseline visual field global indices, and optic disc parameters as measured by HRT. For a subgroup of patients with at least 5 years of follow up and 10 visual field tests, pointwise linear regression analysis (PROGRESSOR for Windows software) was applied to the visual field series. RESULTS:There was no significant difference in the two groups with respect to sex, age at diagnosis, family history of glaucoma, history of ischaemic risk factors and vasospasm, or laterality of glaucoma. The comparison of IOP, CD ratio and visual field global indices, MD and CPSD in the two groups showed no significant difference. There were no differences in the mean values for any of the HRT parameters analysed. For the subgroup of patients with at least 5 years of follow up, there was also no significant difference in the number of patients with progressing locations, the mean number of progressing locations per subject, the mean slope of the progressing locations or the mean slope for whole visual field. CONCLUSIONS:The absence of phenotypic differences in normal tension glaucoma patients with and without the OPA1 polymorphisms IVS 8 +4 C/T; +32 T/C suggest that these OPA1 polymorphisms do not underlie any major phenotypic diversity in these patients.

Project description:Importance:Mutations in the myocilin (MYOC) gene are the most common molecularly defined cause of primary open-angle glaucoma that typically occurs in patients with high intraocular pressures (IOP). One MYOC mutation, p.Gln368Ter, has been associated with as many as 1.6% of primary open-angle glaucoma cases that had a mean maximum recorded IOP of 30 mm Hg. However, to our knowledge, the role of the p.Gln368Ter mutation in patients with normal-tension glaucoma (NTG) with an IOP of 21 mm Hg or lower has not been investigated. Objective:To evaluate the role of the p.Gln368Ter MYOC mutation in patients with NTG. Design, Setting, and Participants:In this case-control study of the prevalence of the p.Gln368Ter mutation in patients with NTG, cohort 1 was composed of 772 patients with NTG and 2152 controls from the United States (Iowa, Minnesota, and New York) and England and cohort 2 was composed of 561 patients with NTG and 2606 controls from the Massachusetts Eye and Ear Infirmary and the NEIGHBORHOOD consortium. Genotyping was conducted using real-time polymerase chain reaction that was confirmed with Sanger sequencing, the imputation of genome-wide association study data, or an analysis of whole-exome sequence data. Data analysis occurred between April 2007 and April 2018. Main Outcomes and Measures:Comparison of the frequency of the p.Gln368Ter MYOC mutation between NTG cases and controls with the Fisher exact test. Results:Of 6091 total participants, 3346 (54.9%) were women and 5799 (95.2%) were white. We detected the p.Gln368Ter mutation in 7 of 772 patients with NTG (0.91%) and 7 of 2152 controls (0.33%) in cohort 1 (P = .03). In cohort 2, we detected the p.Gln368Ter mutation in 4 of 561 patients with NTG (0.71%) and 10 of 2606 controls (0.38%; P = .15). When the cohorts were analyzed as a group, the p.Gln368Ter mutation was associated with NTG (odds ratio, 2.3; 95% CI, 0.98-5.3; P = .04). Conclusions and Relevance:In cohorts 1 and 2, the p.Gln368Ter mutation in MYOC was found in patients with IOPs that were 21 mm Hg or lower (NTG), although at a frequency that is lower than previously detected in patients with higher IOP. These data suggest that the p.Gln368Ter mutation may be associated with glaucoma in patients with normal IOPs as well as in patients with IOPs that are greater than 21 mm Hg.

Dataset Information

No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients.

Purpose

Methods

Results

Conclusions

Publications

No difference in genotype frequencies of polymorphisms of the nitric oxide pathway between Caucasian normal and high tension glaucoma patients.

Similar Datasets

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