title: Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in age-related macular degeneration.
abstract: OBJECTIVE
  We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration (AMD).
  
  
  METHODS
  We enrolled 1388 AMD patients with neovascular AMD or geographic atrophy and 487 unrelated control subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924), and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product of CYP46A1, was quantified by gas chromatography-mass spectrometry using an authentic deuterated internal standard in subgroups of patients and controls. The χ(2) test was used to compare categoric allelic and genotype distributions between cases and controls. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated for AMD risk, and adjusted for age and gender. Significance levels were set at P < 0.05.
  
  
  RESULTS
  The rs754203 SNP in the CYP46A1 gene was not associated with AMD (crude OR = 1.2, 95% CI = 0.9-1.4, P = 0.2). The crude OR for risk of AMD was 2.9 (95% CI = 2.4-3.4, P < 0.0001) according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0 (95% CI = 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI = 1.1-4.1, P = 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene, and carrying no risk alleles in the CFH and LOC387715 genes.
  
  
  CONCLUSIONS
  The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional studies with larger sample sizes are needed in AMD subjects at no risk in CFH and LOC387715.
authors.affiliation: INRA, UMR1324 Centre des Sciences du Goût et de l'Alimentation, Eye & Nutrition Research Group, Dijon, France.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fourgeux
authors.forename: Brice
authors.initials: B
authors.lastname: Dugas
authors.forename: Florence
authors.initials: F
authors.lastname: Richard
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
authors.forename: Niyazi
authors.initials: N
authors.lastname: Acar
authors.forename: Alain M
authors.initials: AM
authors.lastname: Bron
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Korobelnik
authors.forename: Nicolas
authors.initials: N
authors.lastname: Leveziel
authors.forename: Jennyfer
authors.initials: J
authors.lastname: Zerbib
authors.forename: Nathalie
authors.initials: N
authors.lastname: Puche
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Creuzot-Garcher
authors.forename: Eric
authors.initials: E
authors.lastname: Souied
authors.forename: Lionel
authors.initials: L
authors.lastname: Bretillon
mesh_terms: D000368:Aged; D000483:Alleles; D002784:Cholesterol / Q000097:blood; D000072556:Cholesterol 24-Hydroxylase; D017242:Complement Factor H / Q000235:genetics; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D060005:Genotyping Techniques; D057092:Geographic Atrophy / Q000097:blood / Q000235:genetics*; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D013250:Steroid Hydroxylases / Q000235:genetics*; D057135:Wet Macular Degeneration / Q000097:blood / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; C493495:CFH protein, human; D006888:Hydroxycholesterols; D011506:Proteins; C044563:24-hydroxycholesterol; D017242:Complement Factor H; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase