Gareth J McKay1, Ian S Young1, Ann McGinty1, Graham C G Bentham2, Usha Chakravarthy3, Mati Rahu4, Johan Seland5, Gisele Soubrane6, Laura Tomazzoli7, Fotis Topouzis8, Jesus Vioque9, Paulus T V M de Jong10, Astrid E Fletcher11. 1. Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. 2. School of Environmental Sciences, University of East Anglia, Norwich, United Kingdom. 3. Centre for Experimental Medicine, Institute of Clinical Science, Queen's University Belfast, Belfast, United Kingdom. 4. Department of Epidemiology and Biostatistics, National Institute for Health Development, Tallinn, Estonia. 5. Eye Department, University of Bergen, Bergen, Norway. 6. Department of Ophthalmology, Hotel Dieu de Paris, University Paris Descartes-1, Paris, France. 7. Clinica Oculistica, Università degli Studi di Verona, Verona, Italy. 8. Department of Ophthalmology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece. 9. CIBER de Epidemiologia y Salud Publica, Universidad Miguel Hernandez, Alicante, Spain. 10. The Netherlands Institute of Neuroscience, AMC, Amsterdam, The Netherlands. 11. Faculty of Epidemiology & Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom. Electronic address: astrid.fletcher@lshtm.ac.uk.
Abstract
PURPOSE: 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. DESIGN: Population-based, cross-sectional study in a random sample aged 65 years or older from 7 European countries. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: Adjusted odds ratio (OR) for 3 outcomes (early AMD, late AMD, nvAMD). RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. DESIGN: Population-based, cross-sectional study in a random sample aged 65 years or older from 7 European countries. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: Adjusted odds ratio (OR) for 3 outcomes (early AMD, late AMD, nvAMD). RESULTS: 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. CONCLUSIONS: 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: A F Bais; R M Lucas; J F Bornman; C E Williamson; B Sulzberger; A T Austin; S R Wilson; A L Andrady; G Bernhard; R L McKenzie; P J Aucamp; S Madronich; R E Neale; S Yazar; A R Young; F R de Gruijl; M Norval; Y Takizawa; P W Barnes; T M Robson; S A Robinson; C L Ballaré; S D Flint; P J Neale; S Hylander; K C Rose; S-Å Wängberg; D-P Häder; R C Worrest; R G Zepp; N D Paul; R M Cory; K R Solomon; J Longstreth; K K Pandey; H H Redhwi; A Torikai; A M Heikkilä Journal: Photochem Photobiol Sci Date: 2018-02-14 Impact factor: 3.982
Authors: Amy E Millen; Jing Nie; Julie A Mares; Pamela L Lutsey; Michael J LaMonte; Stacy M Meuer; Michelle W Sahli; Christopher A Andrews; Barbara E K Klein; Ronald Klein Journal: Invest Ophthalmol Vis Sci Date: 2019-04-01 Impact factor: 4.799