Abstract
SIX1 and SIX6 are glaucoma susceptibility genes. Previous reports indicate that the single nucleotide polymorphism (SNP) rs33912345 in SIX6 is associated with inferior circumpapillary retinal nerve fibre layer (cpRNFL) thickness (cpRNFLT). Although the region of visual field defect in glaucoma patients is directly related to cpRNFL thinning, a detailed sector analysis has not been performed in genetic association studies. In the present study, we evaluated 26 tagging SNPs in the SIX1/SIX6 locus ±50 kb region in a population of 2,306 Japanese subjects with 4- and 32-sector cpRNFLT analysis. While no SNPs showed a significant association with cpRNFLT in the 4-sectored analysis, the finer 32-sector assessment clearly showed a significant association between rs33912345 in the SIX1/SIX6 locus with inferior cpRNFL thinning at 292.5–303.8° (β = −4.55, P = 3.0 × 10−5). Furthermore, the fine-sectored cpRNFLT analysis indicated that SIX1/SIX6 polymorphisms would affect cpRNFL thinning at 281.3–303.8°, which corresponds to parafoveal scotoma in a visual field test of glaucoma patients.
Highlights
Glaucoma is a complex vision-threatening disorder with a multifactorial aetiology that includes both genetic and environmental factors[1,2,3], and it is one of the most prevalent causes of irreversible blindness worldwide[4]
Our study used a tagging single nucleotide polymorphism (SNP) approach to show that polymorphisms in the SIX1/SIX6 region was significantly associated with inferior circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and marginally associated with superior cpRNFLT in a community-based Japanese cohort
The importance of the SIX1/SIX6 locus in glaucoma was initially discovered by a genome-wide association studies (GWAS) for vertical cup-to-disc ratio (VCDR), and subsequent GWAS for primary open-angle glaucoma (POAG) confirmed the association between polymorphisms in this locus with glaucoma onset[9, 33, 34]
Summary
Glaucoma is a complex vision-threatening disorder with a multifactorial aetiology that includes both genetic and environmental factors[1,2,3], and it is one of the most prevalent causes of irreversible blindness worldwide[4]. Genetic studies on cpRNFLT have shown consistent contributions of the single nucleotide polymorphisms (SNPs) rs33912345 and rs10483727 located within the SIX1/SIX6 loci to cpRNFL thinning in the superior and inferior sectors, but not in the temporal, nasal, and global sectors[30,31,32].
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