LMX1B Locus Associated with Low-Risk Baseline Glaucomatous Features in the POAAGG Study.

Elana Meer,Rebecca Salowe,Ebenezer Daniel,Jie He,Maxwell Pistilli,Harini V Gudiseva,Brendan Mcgeehan,Joan M O’Brien,Gui Shang Ying,Vivian L Qin,Venkata R M Chavali

doi:10.3390/genes12081252

Elana Meer, Rebecca Salowe + Show 9 more

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https://doi.org/10.3390/genes12081252

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Primary open-angle glaucoma (POAG) is the leading cause of irreversible blindness worldwide and has been associated with multiple genetic risk factors. The LMX1B gene is a genetic susceptibility factor for POAG, and several single-nucleotide polymorphisms (SNPs) were shown to be associated with POAG in our own prior Primary Open-Angle African American Glaucoma Genetics (POAAGG) study genome-wide association study (GWAS). This study evaluated the association of the LMX1B locus with baseline optic disc and clinical phenotypic characteristics of glaucoma patients from our African American cohort. Compared to the GG genotype in SNP rs187699205, the GC genotype in this SNP was found to be significantly associated with a smaller cup-to-disc ratio (CDR) and increased (better) visual field mean deviation (MD) in glaucoma cases. None of the glaucoma cases with the GC genotype had disc hemorrhages, disc notching, or beanpot disc appearance. In conclusion, glaucoma phenotypes differed significantly by LMX1B variant in African American patients with POAG, and a SNP variant was associated with certain disease features considered lower risk.

Highlights

Primary open-angle glaucoma (POAG) is a complex neurodegenerative disease characterized by optic nerve atrophy and resultant progressive loss of vision [1,2]
We found that the GC genotype may be associated with features of decreased POAG disease severity in a cohort of African American subjects
Murine studies have shown that Lmx1b mutations cause elevated intraocular pressure (IOP) and glaucomatous nerve damage, both in the presence and in the absence of structural or developmental ocular abnormalities [11]

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Introduction

Primary open-angle glaucoma (POAG) is a complex neurodegenerative disease characterized by optic nerve atrophy and resultant progressive loss of vision [1,2]. POAG has been associated with multiple environmental and genetic risk factors, including elevated intraocular pressure (IOP), advanced age, family history, and African ancestry [3,4]. Recent GWAS studies demonstrated that LMX1B variants are associated with elevated IOP and POAG, even without a diagnosis of NPS or extraocular involvement, and in the absence of anterior segment abnormalities [9]. In our Primary Open-Angle African American Glaucoma Genetics (POAAGG) GWAS study, the variants in LMX1B were significantly associated with mean deviation (MD) baseline, but not with IOP [13]. There have been relatively few studies investigating the genetic risk factors for glaucoma in African American populations, even though this population has a higher prevalence of POAG and more severe outcomes [14,15]

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