title: Associations between Serum Vitamin D and Genetic Variants in Vitamin D Pathways and Age-Related Macular Degeneration in the European Eye Study.
abstract: To study associations between early and late age-related macular degeneration (AMD) and neovascular AMD (nvAMD) with serum 25-hydroxy vitamin D (25(OH)D) and genetic variants in vitamin D pathway genes.
  
  
  
  Population-based, cross-sectional study in a random sample aged 65 years or older from 7 European countries.
  
  
  
  Of 4753 participants, 4496 (2028 men and 2468 women), with a mean age of 73 years, provided a blood sample; 2137 had no signs of AMD, 2209 had early AMD, and 150 had late AMD, of whom 104 had nvAMD.
  
  
  
  Participants were interviewed to determine smoking and alcohol use, sunlight exposure, and diet; underwent fundus photography. Fundus images were graded using the International Classification System for Age-Related Maculopathy. The 25(OH)D was measured by liquid chromatography-tandem mass spectrometry and categorized as deficient (<30 nmol/l), insufficient (30-50 nmol/l), or adequate (≥50 nmol/l). Genotyping was performed on a subsample of 1284 AMD cases and controls for 93 single nucleotide polymorphisms (SNPs) from 7 genes. Associations were investigated by linear or logistic regression adjusted for potential confounders.
  
  
  
  Adjusted odds ratio (OR) for 3 outcomes (early AMD, late AMD, nvAMD).
  
  
  
  No linear association was found with 25(OH)D and early or late AMD or nvAMD. There was no association between insufficient or deficient status with early or late AMD. Deficient status was associated with nvAMD (adjusted OR, 1.27; 95% confidence interval, 1.1-1.45; P < 0.0001). Significant (P < 0.05) associations with 25(OH)D were found for SNPs in genes GC, VDR, CYP2R1, and CYP27B1. Two SNPs (VDR) were associated with early AMD, 4 SNPs (RXRA) and 1 SNP (VDR) were associated with nvAMD, and 1 SNP (RXRA), 2 SNPs (VDR), and 1 SNP (CYP2R1) were associated with late AMD. After Bonferroni correction, no SNPs were associated with early AMD, late AMD, or nvAMD.
  
  
  
  Deficiency in 25(OH)D was associated with nvAMD, but the adjusted OR was small, and we cannot exclude residual confounding. The hypothesis of a causal association of vitamin D with AMD is not supported by clear evidence for an association of vitamin D SNPs with early AMD, late AMD, or nvAMD.
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: McKay
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Young
authors.affiliation: Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Ann
authors.initials: A
authors.lastname: McGinty
authors.affiliation: School of Environmental Sciences, University of East Anglia, Norwich, United Kingdom.
authors.forename: Graham C G
authors.initials: GC
authors.lastname: Bentham
authors.affiliation: Centre for Experimental Medicine, Institute of Clinical Science, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Usha
authors.initials: U
authors.lastname: Chakravarthy
authors.affiliation: Department of Epidemiology and Biostatistics, National Institute for Health Development, Tallinn, Estonia.
authors.forename: Mati
authors.initials: M
authors.lastname: Rahu
authors.affiliation: Eye Department, University of Bergen, Bergen, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Seland
authors.affiliation: Department of Ophthalmology, Hotel Dieu de Paris, University Paris Descartes-1, Paris, France.
authors.forename: Gisele
authors.initials: G
authors.lastname: Soubrane
authors.affiliation: Clinica Oculistica, Università degli Studi di Verona, Verona, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Tomazzoli
authors.affiliation: Department of Ophthalmology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
authors.forename: Fotis
authors.initials: F
authors.lastname: Topouzis
authors.affiliation: CIBER de Epidemiologia y Salud Publica, Universidad Miguel Hernandez, Alicante, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Vioque
authors.affiliation: The Netherlands Institute of Neuroscience, AMC, Amsterdam, The Netherlands.
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.affiliation: Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: astrid.fletcher@lshtm.ac.uk.
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Fletcher
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020256:Choroidal Neovascularization / Q000097:blood / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000097:blood* / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000235:genetics*; D044465:White People
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D