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Tin Aung, Monisha Nongpiur, Shamira A Perera, Tien Yin Wong, Eranga Nishanthie Vithana, Chiea Chuen Khor; Evaluation of primary angle closure glaucoma susceptibility loci in primary angle closure suspects. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2136.
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© ARVO (1962-2015); The Authors (2016-present)
Angle closure is a disease spectrum that starts with narrow angles (primary angle closure suspects [PACS]) and culminates in primary angle closure glaucoma (PACG). The reasons for disease progression from the early stages of the disease to blindness from PACG is yet unknown. Thus far, eight genetic loci has been found to show robust, genome-wide significant association with PACG (Vithana et al, Nature Genetics, 2012 and Khor et al, Nature Genetics, 2016). We hypothesize that the pathogenesis of PACG could in part be due to a narrow anterior chamber angle anatomy to begin with, such as in PACS. We thus set out to investigate whether these PACG associated genetic variants are also associated with PACS.
We collected and genotyped a total of 1397 PACS and 927 controls from Singapore of Chinese ethnicity. PACS cases were defined by the following criteria: the presence of bilaterally narrow drainage angles (inability to visualize the pigmented posterior trabecular meshwork in primary gaze for >180 degrees on gonioscopy) with intraocular pressure <21mmHg and normal optic discs. Control individuals were those with IOP <21 mmHg with open angles and normal optic discs. The 8 SNPs were genotyped by Taqman assays. The association between SNP genotypes and PACS status was measured using logistic regression. A p-value of 0.006 was set to account for the testing of 8 genetic loci using a Bonferroni correction.
Of the 8 loci investigated, SNPs at PCMTD1-ST18, EPDR1 and DPM2-FAM102A were found to be significantly associated with PACS, after adjustment for age and sex. The top associated SNPs were rs1015213 [A] in PCMTD1-ST18 (odds ratio, OR 2.36, p=0.002), rs3816415 [A] in EPDR1 (OR=1.49, p<0.001) and rs3739821 [G] in DPM2-FAM102A (OR=1.40, p<0.001). However, no significant associations were noted for other PACG SNPs rs3753841 (OR 1.15, p = 0.09), rs11024102 (OR 1.02, p = 0.78), rs736893 (OR 0.88, p=0.14), rs1258267 (OR 0.92, p=0.37) and rs7494379 (OR 0.96, p=0.59) in our Chinese PACS subjects.
In our study, 3 of 8 PACG associated loci were significantly associated with PACS, the earliest stage in the angle closure glaucoma disease course. The association of these 3 PACG loci with PACS suggest that these loci may be related to a narrow angle configuration.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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