Purchase this article with an account.
N. Fuse, Y. Mashima, M. Mengkegale, T. Funayama, A. Miyazawa, K. Nishida; Screening for Candidate Genes for Open-angle Glaucoma on Chromosome 2. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5603.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To screen for candidate genes for open-angle glaucoma on chromosome 2, including the GLC1B locus for primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG).
We selected 675 SNPs on chromosome 2, and performed a first case-control study using 368 samples. A second case-control study was performed on 375 samples using 6 selected SNPs. The genes around statistically significant SNPs were chosen for direct screening of the sequences, and 472 unrelated glaucoma patients (POAG 186 cases, NTG 286 cases) and 271 control subjects were studied for sequencing. An informed consent was obtained from all patients.
A statistically significant SNP (rs678350) was located within the Hexokinase 2 (HK2) gene which contained 18 exons and 917 amino acids. The HK2 gene plays an important role in intracellular glucose metabolism by catalyzing the conversion of glucose to glucose-6-phosphate. We screened the coding exons including the intron-exon boundaries, and found 2 coding SNPs; Q142H (A/T) in exon 4 and R844K (G/A) in exon 17. The incidence of Q142H was higher in the NTG group than in the control group (P=0.051), but not higher in the POAG group than in the control group (P=0.471) for the dominant effect of the mutant allele. The allelic frequency of the Q142H (A/T) variant was significantly higher in the NTG group than in the control group (P=0.018), but it was not higher in the POAG group than in the control group (P=0.224). There was no statistically difference between POAG/NTG and R844K. No other mutation was found.
Our findings indicate that there is possibility of an association of the HK2 variant and the pathogenesis of NTG.
This PDF is available to Subscribers Only