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Eranga Nishanthie Vithana, Monisha Esther Nongpiur, Baskaran Mani, Chiea-Chuen Khor, Ching-Yu Cheng, John Allen, Tien Yin Wong, Tin Aung; Investigation of PACG associated genetic variants in persons with early stages of angle closure disease. Invest. Ophthalmol. Vis. Sci. 2016;57(12):807. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Primary angle closure glaucoma (PACG) is classified into three stages: primary angle closure suspects (PACS), primary angle closure (PAC) and PACG. The reasons for disease progression from the early stages of the disease to blindness from PACG is yet unknown. We identified significant association at three genetic loci for PACG; rs11024102 at PLEKHA7, rs3753841 at COL11A1 and rs1015213 at PCMTD1-ST18 on chromosome 8q (Vithana et al, Nature Genetics, 2012). Recently two additional PACG associated loci were dentifed: one within the NUCB2 gene (338 Gln→Glu (rs757081), P = 1.30 x 10-10, OR = 1.14) and another within PXDNL (833 Ser→Asn (rs11985241), P = 2.39 x 10-9, OR= 0.87 (Aung T et al ARVO Meeting Abstracts May 6, 2015. 4383). Here we aimed to investigate whether these PACG associated genetic variants, are also associated with PACS.
We collected a total of 1200 PACS and 943 controls from Singapore of Chinese ethnicity. PACS cases had bilaterally narrow drainage angles with inability to visualize the pigmented posterior trabecular meshwork in primary gaze for >180 degrees on gonioscopy but normal intraocular pressure (IOP) and optic discs. Control individuals were those with IOP ≤ 21 mm Hg with open angles and normal optic discs. The 5 SNPs were genotyped in cases and controls by Taqman assays. The association between SNP genotypes and PACS status was measured using logistic regression. A p-value of 0.01 was set to account for the testing of 5 genetic loci using a Bonferroni correction.
Only 2 of the 5 SNPs investigated showed experimentally significant associations with PACS, after adjustment for age and sex. The top associated SNPs were rs1015213 [T] at PCMTD1-ST18 (OR=) 2.26, p = 0.004) and rs757081 [G] in NUCB2 (OR=1.22, P= 0.008). However, no significant associations were noted for SNPs rs3753841 (OR 1.13, p = 0.15), rs11985241 (OR=0.86, p = 0.087) and rs11024102 (OR 1.05, p = 0.53) in our Chinese PACS subjects, despite these SNPs showing significant association (p < 0.05) with a similar sized cohort (N=980) of Chinese PACG subjects.
In our study, the PACG associated SNPs rs1015213 and rs757081 were significantly associated with PACS, the earliest stage in the angle closure glaucoma disease course. Evaluation of the genetic biomarkers may help in early recognition of subjects at risk for development of PACG.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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