Paun, Constantin C., Ersoy, Lebriz, Schick, Tina, Groenewoud, Joannes M. M., Lechanteur, Yara T., Fauser, Sascha, Hoyng, Carel B., de Jong, Eiko K. and den Hollander, Anneke I. (2015). Genetic Variants and Systemic Complement Activation Levels Are Associated With Serum Lipoprotein Levels in Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci., 56 (13). S. 7766 - 7774. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. Genetic variants in genes encoding components of lipid metabolism have been associated with AMD. The aims of this study were to evaluate the relation of these genetic variants with serum lipid levels in AMD) in a large case-control cohort (n = 3070) and to test for correlations between lipids and complement activation. METHODS. Single nucleotide polymorphisms (SNPs) in eight lipid metabolism genes, previously described to be associated with AMD, were genotyped and tested for their association in our case-control cohort. Serum apolipoprotein B (ApoB), apolipoprotein AI (Apo-AI), cholesterol, triglycerides (TG), high-density lipoprotein-cholesterol (HIM!), and complement activation levels (C3d/C3) were measured and tested for association with AMD. Non-HDL cholesterol and LDL were inferred based on the measurements of the other lipids and lipoproteins. General linear models and chi(2) tests were used to evaluate the relation of SNPs and lipids/lipoproteins to the disease as well as their interrelations. RESULTS. Significant genotypic associations with AMD were observed for SNPs in CETP, APOE, and FADS1. The serum levels of Apo-AI and HDLC were significantly higher in patients compared with controls. Triglycerides (TG) levels were lower in AMD compared with controls. A cumulative effect was observed for APOE and CETP genotypes on HDLC and Apo-AI levels. Complement activation levels correlated positively with HDLC and Apo-AI, and negatively with TG. Both the lipids/lipoproteins and the complement activation levels associate independently to AMI). CONCLUSIONS. This study bridges the gap between genetic associations and physiological lipid levels in MID. Additionally, the observed correlations between complement activation and lipid levels link two major systems that previously were always assessed independently.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Paun, Constantin C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ersoy, LebrizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schick, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Groenewoud, Joannes M. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lechanteur, Yara T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fauser, SaschaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoyng, Carel B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
de Jong, Eiko K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
den Hollander, Anneke I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-384769
DOI: 10.1167/iovs.15-17035
Journal or Publication Title: Invest. Ophthalmol. Vis. Sci.
Volume: 56
Number: 13
Page Range: S. 7766 - 7774
Date: 2015
Publisher: ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication: ROCKVILLE
ISSN: 1552-5783
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TRANSFER PROTEIN-DEFICIENCY; PIGMENT EPITHELIAL-CELLS; GENOME-WIDE ASSOCIATION; RISK-FACTORS; CARDIOVASCULAR-DISEASE; APOLIPOPROTEIN-E; LIPID-LEVELS; CHOLESTEROL; PLASMA; APOEMultiple languages
OphthalmologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38476

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