Dataset Information

Positive association of common variants in CD36 with neovascular age-related macular degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is a leading cause of legal blindness among older individuals of industrialized countries. In neovascular AMD, which is an advanced stage of AMD, choroidal neovascularization develops underneath the macula and destroys central vision. Oxidative stress is a hypothesized pathway for the pathophysiology of AMD. CD36 was chosen as a candidate gene for neovascular AMD because the protein plays an important role in this pathway as well as in angiogenesis and in maintaining chorioretinal homeostasis. We tested 19 tag single nucleotide polymorphisms (SNPs) across CD36 for their association with the disease in a Japanese population comprising 109 neovascular AMD subjects and 182 unrelated controls. Five of the 19 SNPs demonstrated a nominally significant association with neovascular AMD (P < 0.05), of which two (rs3173798 and rs3211883) withstood Bonferroni correction for multiple testing (rs3173798, nominal P = 9.96 x 10-4, allele-specific odds ratio = 0.55; rs3211883, nominal P = 2.09 x 10-4, allele-specific odds ratio = 0.50). Population structure analyses excluded stratification artifacts in our study cohort. This study supports the candidacy of CD36 as a novel susceptibility gene for neovascular AMD. Replication of our results in other populations will provide further convincing evidence for the genetic association.

SUBMITTER: Kondo N

PROVIDER: S-EPMC2806007 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature

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Positive association of common variants in CD36 with neovascular age-related macular degeneration.

Kondo Naoshi N Honda Shigeru S Kuno Shin-Ichi S Negi Akira A

Aging 20090212 2

Age-related macular degeneration (AMD) is a leading cause of legal blindness among older individuals of industrialized countries. In neovascular AMD, which is an advanced stage of AMD, choroidal neovascularization develops underneath the macula and destroys central vision. Oxidative stress is a hypothesized pathway for the pathophysiology of AMD. CD36 was chosen as a candidate gene for neovascular AMD because the protein plays an important role in this pathway as well as in angiogenesis and in m ...[more]

PMID: 20157514

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Project description:PurposeTo determine if plasma metabolic profiles can detect differences between patients with neovascular age-related macular degeneration (NVAMD) and similarly-aged controls.MethodsMetabolomic analysis using liquid chromatography with Fourier-transform mass spectrometry (LC-FTMS) was performed on plasma samples from 26 NVAMD patients and 19 controls. Data were collected from mass/charge ratio (m/z) 85 to 850 on a Thermo LTQ-FT mass spectrometer, and metabolic features were extracted using an adaptive processing software package. Both non-transformed and log2 transformed data were corrected using Benjamini and Hochberg False Discovery Rate (FDR) to account for multiple testing. Orthogonal Partial Least Squares-Discriminant Analysis was performed to determine metabolic features that distinguished NVAMD patients from controls. Individual m/z features were matched to the Kyoto Encyclopedia of Genes and Genomes database and the Metlin metabolomics database, and metabolic pathways associated with NVAMD were identified using MetScape.ResultsOf the 1680 total m/z features detected by LC-FTMS, 94 unique m/z features were significantly different between NVAMD patients and controls using FDR (q = 0.05). A comparison of these features to those found with log2 transformed data (n = 132, q = 0.2) revealed 40 features in common, reaffirming the involvement of certain metabolites. Such metabolites included di- and tripeptides, covalently modified amino acids, bile acids, and vitamin D-related metabolites. Correlation analysis revealed associations among certain significant features, and pathway analysis demonstrated broader changes in tyrosine metabolism, sulfur amino acid metabolism, and amino acids related to urea metabolism.ConclusionsThese data suggest that metabolomic analysis can identify a panel of individual metabolites that differ between NVAMD cases and controls. Pathway analysis can assess the involvement of certain metabolic pathways, such as tyrosine and urea metabolism, and can provide further insight into the pathophysiology of AMD.

Dataset Information

Positive association of common variants in CD36 with neovascular age-related macular degeneration.

Publications

Positive association of common variants in CD36 with neovascular age-related macular degeneration.

Similar Datasets

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