title: Evaluation of nine candidate genes in patients with normal tension glaucoma: a case control study.
abstract: BACKGROUND
  Normal 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.
  
  
  METHODS
  Ninety-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.
  
  
  RESULTS
  Results 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.
  
  
  CONCLUSIONS
  Common variants of OPTN, PARL, MFN1 and MFN2 should be analysed in other cohorts to confirm their involvement in normal tension glaucoma.
authors.affiliation: Centre for Ophthalmology, Institute for Ophthalmic Research, Molecular Genetics Laboratory, Tuebingen, Germany. cwolf@mpipsykl.mpg.de
authors.forename: Christiane
authors.initials: C
authors.lastname: Wolf
authors.forename: Eugen
authors.initials: E
authors.lastname: Gramer
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Francesca
authors.initials: F
authors.lastname: Pasutto
authors.forename: Eva
authors.initials: E
authors.lastname: Reinthal
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Nicole
authors.initials: N
authors.lastname: Weisschuh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers