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Genetic association of SIX1 gene variants and primary open‐angle glaucoma in Caucasians
Author(s) -
Shaw Robert,
Wang Ye,
Chen Yuhong,
Du Hongjn,
Zhang Kang
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.928.12
Subject(s) - glaucoma , open angle glaucoma , genome wide association study , optic nerve , ophthalmology , single nucleotide polymorphism , medicine , pathogenesis , intraocular pressure , allele , etiology , genetic association , retinal ganglion cell , genetics , pathology , genotype , biology , gene
Primary open‐angle glaucoma (POAG) is a condition of disorders that have optic nerve damage and slow progressive degeneration of retina ganglion cells, causing irreversible defects in the visual field loss usually associated with elevated intraocular pressure (IOP). The exact mechanism for the pathogenesis of POAG is still largely unknown. However, studies have shown that POAG has a multifactorial etiology, including genetics, high IOP and central corneal thickness (CCT). Recently, genome‐wide association study (GWAS) identified a common variant (rs10483727) on chromosome 14q22.3‐q23 within 40kbp of the SIX1 gene significantly associated with vertical cup‐disc ratio (VCDR), a parameter in the clinical assessment of the glaucoma management. To investigate the association of SIX1 gene variants with POAG, we genotyped a Caucasian cohort with 768 cases and 815 age and ethnicity matched controls. For the four SNPs we tested near SIX1 gene, we found that rs10483727 showed significant association with POAG in the Caucasian cohort (p = 9.82 × 10–6 for an additive model, OR =1.37 (1.19 – 1.59); T allele: 45.4% in cases versus 37.7% in controls). To confirm our association study result, we induced a mechanical injury to the axon by optic nerve crush in mice and found the expression of SIX1 was increased in nerve injured mice. This study was supported by grants from NIH/NEI to KZ.