Abstract
BackgroundNormal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. Monogenic forms following classical inheritance patterns are rare in this glaucoma subtype. Instead, multigenic inheritance is proposed for the majority of cases. The present study tested common sequence variants in candidate genes for association with normal tension glaucoma in the German population.MethodsNinety-eight SNPs were selected to tag the common genetic variation in nine genes, namely OPTN (optineurin), RDX (radixin), SNX16 (sorting nexin 16), OPA1 (optic atrophy 1), MFN1 (mitofusin 1), MFN2 (mitofusin 2), PARL (presenilin associated, rhomboid-like), SOD2 (superoxide dismutase 2, mitochondrial) and CYP1B1 (cytochrome P450, family 1, subfamily B, polypeptide 1). These SNPs were genotyped in 285 cases and 282 fully evaluated matched controls. Statistical analyses comprised single polymorphism association as well as haplogroup based association testing.ResultsResults suggested that genetic variation in five of the candidate genes (RDX, SNX16, OPA1, SOD2 and CYP1B1) is unlikely to confer major risk to develop normal tension glaucoma in the German population. In contrast, we observed a trend towards association of single SNPs in OPTN, MFN1, MFN2 and PARL. The SNPs of OPTN, MFN2 and PARL were further analysed by multimarker haplotype-based association testing. We identified a risk haplotype being more frequent in patients and a vice versa situation for the complementary protective haplotype in each of the three genes.ConclusionCommon variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.
Highlights
Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population
We found no evidence of association between normal tension glaucoma (NTG) and RDX, SNX16, OPA1, SOD2 and CYP1B1
Our study based on the genotyping of tagging single nucleotide polymorphism (tagSNP) to maximize genetic coverage of nine candidate genes (OPTN, RDX, SNX16, OPA1, MFN1, MFN2, PARL, SOD2 and CYP1B1)
Summary
Normal tension glaucoma is a major subtype of glaucoma, associated with intraocular pressures that are within the statistically normal range of the population. The three major risk factors for the development of glaucoma are elevated intraocular pressure (IOP), advanced age and a positive family history. It is estimated, that by 2010, 60 million people will suffer from glaucoma and that the disease will be the second leading cause of blindness worldwide [1]. In approximately one third of all Caucasian POAG patients the IOP is within the average range of 10-21 mmHg. In approximately one third of all Caucasian POAG patients the IOP is within the average range of 10-21 mmHg Such patients with normal tension glaucoma (NTG) show typical pathological cupping of the optic nerve as well as characteristic visual field defects [2,3]
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