title: Analysis of three pigment epithelium-derived factor gene polymorphisms in patients with exudative age-related macular degeneration.
abstract: OBJECTIVE
  Exudative age-related macular degeneration (exudative AMD) is a common vision-threatening disease, with both environmental and genetic factors contributing to its development. Recently, homozygosity for the 72Met variant of the pigment epithelium-derived factor (PEDF) Met72Thr gene polymorphism (rs1136287) was identified as a novel risk factor for exudative AMD in Chinese patients from Taiwan. The role of this polymorphism, however, has not yet been determined in a white European population. In addition, two other PEDF gene polymorphisms, -5736T>C (rs12150053) and -5304C>T (rs12948385), have been associated with increased risk of diabetic retinopathy, but have not yet been studied among patients with exudative AMD. The purpose of the present study was thus to investigate a hypothesized association between these PEDF polymorphisms and the presence of exudative AMD in a white European population.
  
  
  METHODS
  The present case-control study comprised 269 patients with exudative AMD and 155 control subjects. Genotypes of the PEDF polymorphisms were determined by 5'-exonuclease assays (TaqMan).
  
  
  RESULTS
  PEDF genotype and allele frequencies were not significantly different between AMD patients and control subjects. The two promoter polymorphisms, -5736T>C (rs12150053) and -5304C>T (rs12948385), were in complete association. Presence of the homozygous PEDF 72 Met/Met genotype was associated with a nonsignificant odds ratio of 1.00 (95% confidence interval: 0.67-1.49, p=0.99). Similarly, presence of the homozygous PEDF -5736 TT genotype or -5304 CC genotype was associated with a nonsignificant odds ratio of 0.99 (95% confidence interval: 0.56 - 1.75, p=0.97). Both promoter polymorphisms were in linkage disequilibrium with the Met72Thr (rs1136287) polymorphism (D'=0.83) and formed three common and one rare haplotype. Haplotype frequencies were similar between AMD patients and control subjects (p>0.05).
  
  
  CONCLUSIONS
  Our data suggest that none of the investigated PEDF polymorphisms is likely a major risk factor for exudative AMD in a white European population.
authors.affiliation: Department of Ophthalmology, Medical University of Graz, Austria. di.mattes@meduni-graz.at
authors.forename: Dietmar
authors.initials: D
authors.lastname: Mattes
authors.forename: Anton
authors.initials: A
authors.lastname: Haas
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Iris
authors.initials: I
authors.lastname: Steinbrugger
authors.forename: Yosuf
authors.initials: Y
authors.lastname: El-Shabrawi
authors.forename: Andreas
authors.initials: A
authors.lastname: Wedrich
authors.forename: Christoph
authors.initials: C
authors.lastname: Werner
authors.forename: Otto
authors.initials: O
authors.lastname: Schmut
authors.forename: Martin
authors.initials: M
authors.lastname: Weger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012044:Regression Analysis; D015843:Serpins / Q000235:genetics*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor