CDKN2B-AS1 genotype-glaucoma feature correlations in primary open-angle glaucoma patients from the United States

Am J Ophthalmol. 2013 Feb;155(2):342-353.e5. doi: 10.1016/j.ajo.2012.07.023. Epub 2012 Oct 27.

Abstract

Purpose: To assess the association between single nucleotide polymorphisms (SNPs) of the gene region containing cyclin-dependent kinase inhibitor 2B antisense noncoding RNA (CDKN2B-AS1) and glaucoma features among primary open-angle glaucoma (POAG) patients.

Design: Retrospective observational case series.

Methods: We studied associations between 10 CDKN2B-AS1 SNPs and glaucoma features among 976 POAG cases from the Glaucoma Genes and Environment (GLAUGEN) study and 1971 cases from the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium. For each patient, we chose the feature from the eye with the higher value. We created cohort-specific multivariable models for glaucoma features and then meta-analyzed the results.

Results: For 9 of the 10 protective CDKN2B-AS1 SNPs with minor alleles associated with reduced disease risk (eg, the G allele at rs2157719), POAG patients carrying these minor alleles had smaller cup-to-disc ratio (0.05 units smaller per G allele at diagnosis; 95% CI: -0.08, -0.03; P = 6.23E-05) despite having higher intraocular pressure (IOP) (0.70 mm Hg higher per G allele at DNA collection; 95% CI: 0.40, 1.00; P = 5.45E-06). For the 1 adverse rs3217992 SNP with minor allele A associated with increased disease risk, POAG patients with A alleles had larger cup-to-disc ratio (0.05 units larger per A allele at diagnosis; 95% CI: 0.02, 0.07; P = 4.74E-04) despite having lower IOP (-0.57 mm Hg per A allele at DNA collection; 95% CI: -0.84, -0.29; P = 6.55E-05).

Conclusion: Alleles of CDKN2B-AS1 SNPs, which influence risk of developing POAG, also modulate optic nerve degeneration among POAG patients, underscoring the role of CDKN2B-AS1 in POAG.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Chromosomes, Human, Pair 9 / genetics
  • Female
  • Genotype
  • Glaucoma, Open-Angle / diagnosis
  • Glaucoma, Open-Angle / genetics*
  • Humans
  • Intraocular Pressure
  • Male
  • Middle Aged
  • Optic Disk / pathology
  • Optic Nerve Diseases / diagnosis
  • Optic Nerve Diseases / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • RNA, Long Noncoding / genetics*
  • Retrospective Studies
  • Trabeculectomy
  • United States
  • Visual Fields

Substances

  • ANRIL long non-coding RNA, human
  • RNA, Long Noncoding

Grant support