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Assessing Early Stage Open-Angle Glaucoma in Patients by Isolated-Check Visual Evoked Potential
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Association of eNOS polymorphisms with primary angle-closure glaucoma.

Mona S Awadalla1, Suman S Thapa, Alex W Hewitt

  • 1Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. awad0002@flinders.edu.au

Investigative Ophthalmology & Visual Science
|February 21, 2013
PubMed
Summary

Genetic variations in the Endothelial nitric oxide synthase (eNOS) gene are associated with primary angle-closure glaucoma (PACG). This study investigated CYP1B1, eNOS, and NTF4 gene associations with PACG in Australian and Nepalese populations.

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Area of Science:

  • Ophthalmology
  • Genetics
  • Molecular Biology

Background:

  • Primary angle-closure glaucoma (PACG) is a significant cause of vision loss worldwide.
  • Genetic factors are implicated in PACG pathogenesis, with several candidate genes investigated across diverse ethnic groups.

Purpose of the Study:

  • To investigate the association between genetic variations in Cytochrome P450 (CYP1B1), Endothelial nitric oxide synthase (eNOS), and Neurotrophin-4 (NTF4) genes and PACG.
  • To compare these genetic associations in Australian and Nepalese populations.

Main Methods:

  • Genotyping of tag single nucleotide polymorphisms (SNPs) in CYP1B1, eNOS, and NTF4 genes.
  • Analysis of 235 PACG patients and 492 controls from Australia and Nepal.
  • Allele, haplotype, and association analyses using PLINK with Bonferroni correction for multiple testing.

Main Results:

  • A significant association between an eNOS SNP (rs3793342) and PACG was found in the Australian cohort (P=0.003).
  • Adjusting for covariates, rs3793342 and rs7830 in eNOS remained significant.
  • An eNOS haplotype showed a global significant association (P=0.019), with CGCAATC demonstrating a specific association (P=0.008).
  • Borderline associations were observed for CYP1B1 and NTF4 in the Nepalese cohort, but did not reach statistical significance after correction.

Conclusions:

  • Common variations in the eNOS gene are likely involved in the pathogenesis of PACG.
  • Population-specific differences in genetic associations were observed between Australian and Nepalese cohorts.
  • Further replication studies in diverse populations are warranted to confirm these findings.