advertisement
Abstract #25275 Published in IGR 12-1
OPA1 increases the risk of normal but not high tension glaucoma
Yu-Wai-Man P; Stewart J D; Hudson G; Andrews R M; Griffiths P G; Birch M K; Chinnery P FJournal of Medical Genetics 2010; 47: 120-125
See also comment(s) by Jonathan Crowston •
Background: Primary open angle glaucoma is a progressive optic neuropathy characterised by the selective loss of retinal ganglion cells, pathological optic disc cupping and visual field defects. The OPA1 gene encodes an inner mitochondrial membrane protein crucial for normal mitochondrial function, and pathogenic mutations cause autosomal dominant optic atrophy by specifically targeting retinal ganglion cells. This raises the distinct possibility that more subtle genetic variations in OPA1 could alter the risk of developing glaucoma. Methods: 137 patients with primary open angle glaucoma (67 patients with high-tension glaucoma (HTG), 70 patients with normal-tension glaucoma (NTG)) and 75 controls from the North East of England were studied. Three single-nucleotide polymorphisms in intron 8 (IVS8+4c->t and IVS8+32t->c) and exon 4 (c.473A->G) of the OPA1 gene were genotyped in the study group. In addition, the entire OPA1 coding region was sequenced in 24 individuals with the CT/TT compound genotype using standard BigDye chemistries. Results: There was no difference in either allele or genotype frequency for the IVS8+32t->c single-nucleotide polymorphisms between patients and controls, but there was a significant association between the T allele at IVS8+4c->t and the risk of developing NTG (OR=2.04, 95% CI=1.10 to 3.81, p=0.004), but not HTG. Logistic regression analysis also confirmed a strong association between the CT/TT compound genotype at IVS8+4 and IVS8+32 with NTG (OR=29.75, 95% CI=3.83 to 231.21, p=0.001). Conclusions: The CT/TT compound genotype at IVS8+4 and IVS8+32 is a strong genetic risk determinant for NTG but not HTG.
P. F. Chinnery. Mitochondrial Research Group, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, United Kingdom. p.f.chinnery@ncl.ac.uk
Classification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
9.2.4 Normal pressure glaucoma (Part of: 9 Clinical forms of glaucomas > 9.2 Primary open angle glaucomas)
