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Danyi Wang, Baojian Fan, Yutao Liu, Michael Hauser, R Rand Allingham, Jonathan Haines, Janey Wiggs; COCH Variants are not Associated with Primary-open Angle Glaucoma or Intraocular Pressure in Caucasians. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6208. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
COCH produces Cochlin, an extracellular matrix protein that has been identified in glaucomatous TM tissue in both humans and mice. Recently, a transgene carrying a copy of the human COCH gene was shown to cause an increase in IOP in monkey organ cultured anterior segments, suggesting that increased expression of COCH in TM could lead to an increase in IOP. The human COCH gene is located on chromosome 14q12, a genomic region that has been implicated in POAG by genetic linkage studies. The purpose of this study is to assess the association between single nucleotide polymorphisms (SNPs) in the COCH gene region on chromosome 14q12 in relation to primary open angle glaucoma (POAG).
539 POAG cases and 336 controls from the Massachusetts Eye and Ear Infirmary (MEEI) were initially genotyped for 16 tag SNPs capturing 100% of COCH alleles with mean r-square of 0.95. Three SNPs of interest in the proximal gene region were genotyped in a second independent group of 518 POAG cases and 445 controls from Duke University Medical Center. Association analysis was performed for POAG overall as well as subgroup analysis after stratifying by IOP.
A significant association was not found between any of the COCH gene SNPs and POAG overall. In subgroup analysis after stratifying by highest IOP, suggestive association between rs8015095 and IOP was found in both the MEEI [p= 0.038, OR 1.55 (1.03-2.33)] and Duke cohorts[(p=0.014, OR 2.01 (1.19-3.41)], and in a meta-analysis (p=0.0011, OR 1.71), however a linear regression analysis did not find an association between the risk allele and IOP level.
Based on function and expression, COCH is an excellent candidate gene for glaucoma. Our study however, did not reveal statistically significant associations between POAG overall or IOP with SNPs in the gene region in this population. It is possible that rare variants in COCH gene may contribute to POAG and IOP level.
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