title: Association of variants in the LIPC and ABCA1 genes with intermediate and large drusen and advanced age-related macular degeneration.
abstract: OBJECTIVE
  Intermediate and large drusen usually precede advanced age-related macular degeneration (AMD). There is little information about which genes influence drusen accumulation. Discovery of genetic variants associated with drusen may lead to prevention and treatments of AMD in its early stages.
  
  
  METHODS
  A total of 3066 subjects were evaluated on the basis of ocular examinations and fundus photography and categorized as control (n = 221), intermediate drusen (n = 814), large drusen (n = 949), or advanced AMD (n = 1082). SNPs in the previously identified CFH, C2, C3, CFB, CFI, APOE, and ARMS2/HTRA1 genes/regions and the novel genes LIPC, CETP, and ABCA1 in the high-density lipoprotein (HDL) cholesterol pathway were genotyped. Associations between stage of AMD and SNPs were assessed using logistic regression.
  
  
  RESULTS
  Controlling for age, sex, education, smoking, body mass index, and antioxidant treatment, the number of minor (T) alleles of the genes LIPC and ABCA1 were significantly associated with a reduced risk of intermediate drusen (LIPC [P trend = 0.045], ABCA1 [P = 4.4 × 10(-3)]), large drusen (LIPC [P = 0.041], ABCA1 [P = 7.7 × 10(-4)]), and advanced AMD (LIPC [P = 1.8 × 10(-3)], ABCA1 [P = 3 × 10(-4)]). After further adjustment for known genetic factors, the protective effect of the TT genotype was significant for intermediate drusen (LIPC [odds ratio (OR), 0.56; 95% confidence interval (CI), 0.33-0.94], ABCA1 [OR, 0.48; 95% CI, 0.27-0.85]), large drusen (LIPC [OR, 0.58; 95% CI, 0.34-0.98)], ABCA1 [OR, 0.41; 95% CI, 0.23-0.74)]), and advanced AMD (LIPC [OR, 0.39; 95% CI, 0.21-0.74)], ABCA1 [OR, 0.35; 95% CI, 0.17-0.71)]). CFH, C3, C2, and ARMS2/HTRA1 were associated with large drusen and advanced AMD.
  
  
  CONCLUSIONS
  LIPC and ABCA1 are related to intermediate and large drusen, as well as advanced AMD. CFH, C3, C2, and ARMS2/HTRA1 are associated with large drusen and advanced AMD. Genes may have varying effects on different stages of AMD.
authors: Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts Medical Center, Boston, Massachusetts, USA.
authors: Yi
authors: Y
authors: Yu
authors: Robyn
authors: R
authors: Reynolds
authors: Jesen
authors: J
authors: Fagerness
authors: Bernard
authors: B
authors: Rosner
authors: Mark J
authors: MJ
authors: Daly
authors: Johanna M
authors: JM
authors: Seddon
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008268:Macular Degeneration / Q000235:genetics* / Q000473:pathology; D008297:Male; D015594:Optic Disk Drusen / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; C504173:LIPC protein, human; D008049:Lipase