title: Primary open-angle glaucoma: association with cholesterol 24S-hydroxylase (CYP46A1) gene polymorphism and plasma 24-hydroxycholesterol levels.
abstract: OBJECTIVE
  Genetics has made significant contributions to the study of glaucoma over the past few decades. Cholesterol-24S-hydroxylase (CYP46A1) is a cholesterol-metabolizing enzyme that is especially expressed in retinal ganglion cells. CYP46A1 and its metabolic product, 24S-hydroxycholesterol, have been linked to neurodegeneration. A single-nucleotide polymorphism (SNP) in the CYP46A1 gene, designated as rs754203 and associated with Alzheimer disease, was evaluated as a genetic risk factor for primary open-angle glaucoma (POAG), as well as plasma 24S-hydroxycholesterol levels.
  
  
  METHODS
  The frequency of the CYP46*C and CYP46*T alleles was analyzed in 150 patients with POAG and 118 control subjects. Plasma 24S-hydroxycholesterol levels were quantified. Sex, age, alleles, and genotype frequencies between patients with POAG and control subjects were compared by using the chi(2) and Student's t-tests. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression to assess the relative association between disease and age, sex, and genotypes.
  
  
  RESULTS
  The frequency of the TT genotype was significantly higher in patients with POAG than in control subjects (61.3% versus 48.3%, respectively, OR = 1.26; 95% CI = 1.006-1.574, P < 0.05). Plasma 24S-hydroxycholesterol levels did not differ between control subjects and patients with POAG. The ratio of estimated brain weight to liver volume as an estimate of the capacity of the human body to synthesize and metabolize 24S-hydroxycholesterol was found to correlate to plasma 24S-hydroxycholesterol in control subjects and patients with POAG.
  
  
  CONCLUSIONS
  The rs754203 SNP in CYP46A1 was associated with a risk for POAG. This polymorphism was not associated with changes in plasma 24S-hydroxycholesterol, highlighting that despite its retinal origin, 24S-hydroxycholesterol cannot be used as a biomarker for POAG.
authors: Eye and Nutrition Research Group, UMR1129 FLAVIC (Flaveur, vision et comportement du consommateur; Flavor, Vision, and Consumer Behavior), INRA (French National Institute for Agricultural Research), Dijon, France.
authors: Cynthia
authors: C
authors: Fourgeux
authors: Lucy
authors: L
authors: Martine
authors: Ingemar
authors: I
authors: Björkhem
authors: Ulf
authors: U
authors: Diczfalusy
authors: Corinne
authors: C
authors: Joffre
authors: Niyazi
authors: N
authors: Acar
authors: Catherine
authors: C
authors: Creuzot-Garcher
authors: Alain
authors: A
authors: Bron
authors: Lionel
authors: L
authors: Bretillon
mesh_terms: D000368:Aged; D000072556:Cholesterol 24-Hydroxylase; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D005902:Glaucoma, Open-Angle / Q000097:blood* / Q000235:genetics*; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D007438:Introns / Q000235:genetics; D008297:Male; D013058:Mass Spectrometry; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011865:Radioisotope Dilution Technique; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase