Associations between Serum Vitamin D and Genetic Variants in Vitamin D Pathways and Age-Related Macular Degeneration in the European Eye Study

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• 作者：Gareth J. McKay ; PhD¹ ; Ian S. Young ; MD¹ ; Ann McGinty ; PhD¹ ; Graham C.G. Bentham ; MA² ; Usha Chakravarthy ; MD³ ; Mati Rahu ; PhD⁴ ; Johan Seland ; MD⁵ ; Gisele Soubrane ; MD⁶ ; Laura Tomazzoli ; MD⁷ ; Fotis Topouzis ; MD⁸ ; Jesus Vioque ; MD⁹ ; Paulus T.V.M. de Jong ; MD¹⁰ ; Astrid E. Fletcher ; PhD¹¹ ; ^{astrid.fletcher@lshtm.ac.uk}
• 关键词：25(OH)D ; 25-hydroxy vitamin D ; AMD ; age-related macular degeneration ; CI ; confidence interval ; GA ; geographic atrophy ; HWE ; Hardy&ndash ; Weinberg equilibrium ; nvAMD ; neovascular age-related macular degeneration ; OR ; odds ratio ; SNP ; single nucleotide polymorphism ; UVB ; ultraviolet B ; VDR ; vitamin D receptor
• 刊名：Ophthalmology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：124
• 期：1
• 页码：90-96
• 全文大小：278 K
• 卷排序：124

文摘

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.DesignPopulation-based, cross-sectional study in a random sample aged 65 years or older from 7 European countries.ParticipantsOf 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.MethodsParticipants 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 MeasuresAdjusted odds ratio (OR) for 3 outcomes (early AMD, late AMD, nvAMD).ResultsNo 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.ConclusionsDeficiency 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.