Genetic Link Identified for Multiple Forms of Glaucoma

Genes may interact through transforming growth factor beta signaling pathway

MONDAY, April 30 (HealthDay News) -- Two genomic regions have been identified that are associated with normal-pressure glaucoma (NPG) and optic nerve disease in exfoliation-syndrome glaucoma (ESG), possibly through the transforming growth factor beta (TGF-beta) signaling pathway, according to a study published online April 26 in PLoS Genetics.

Janey L. Wiggs, M.D., Ph.D., from the Massachusetts Eye and Ear Infirmary in Boston, and colleagues performed a meta-analysis using data from two independent genome-wide association studies for primary open angle glaucoma (POAG), including 3,146 cases and 3,487 controls, followed by subgroup analysis of NPG (defined by intraocular pressure of less than 22 mm Hg). The single-nucleotide polymorphisms that demonstrated the most significant associations were also tested for correlation with ESG.

In meta-analysis of the two POAG datasets, the researchers identified significant associations between two loci (the CDKN2BAS region on 9p21 [rs2157719] and the SIX1/SIX6 region on chromosome 14q23 [rs10483727]) and POAG (odds ratio [OR] for G and A allele, 0.69 and 1.32, respectively). In sub-group analysis, two loci (9p21 containing the CDKN2BAS gene [rs2157719] and a probable regulatory region on 8q22 [rs284489]) were significantly associated with NPG (OR for G and G allele, 0.58 and 0.62, respectively). Both NPG loci were also minimally associated with ESG (OR, 0.59 [P = 0.004] and 0.76 [P = 0.021], respectively). Both loci influenced TGF-beta signaling, and genomic pathway analysis indicated a correlation between TGF-beta and NPG.

"These results suggest that neuro-protective therapies targeting TGF-beta signaling could be effective for multiple forms of glaucoma," the authors write.

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