Genetic Link Identified for Multiple Forms of Glaucoma
(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.
Janey L. Wiggs, MD, PhD, 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 <22mmHg). 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.