Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.
Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 in...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3968152?pdf=render |
| _version_ | 1819227970934407168 |
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| author | Tina Ristau Constantin Paun Lebriz Ersoy Moritz Hahn Yara Lechanteur Carel Hoyng Eiko K de Jong Mohamed R Daha Bernd Kirchhof Anneke I den Hollander Sascha Fauser |
| author_facet | Tina Ristau Constantin Paun Lebriz Ersoy Moritz Hahn Yara Lechanteur Carel Hoyng Eiko K de Jong Mohamed R Daha Bernd Kirchhof Anneke I den Hollander Sascha Fauser |
| author_sort | Tina Ristau |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002), higher age (p = 1.56 × 10(-7)), AMD phenotype (p = 1.15 × 10(-11)) and the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower C3d/C3 ratios were found for diabetes (p = 2.87 × 10(-6)), higher body mass index (p = 1.00 × 10(-13)), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003), rs12144939 (p = 4.60 × 10(-6)) in CFH, rs4151667 (p = 1.01 × 10(-5)) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation. |
| first_indexed | 2024-12-23T10:49:51Z |
| format | Article |
| id | doaj.art-147c59a2f92140ccbb2c00af301c742f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T10:49:51Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-147c59a2f92140ccbb2c00af301c742f2022-12-21T17:49:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9345910.1371/journal.pone.0093459Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels.Tina RistauConstantin PaunLebriz ErsoyMoritz HahnYara LechanteurCarel HoyngEiko K de JongMohamed R DahaBernd KirchhofAnneke I den HollanderSascha FauserAge-related macular degeneration (AMD) is a common condition that leads to severe vision loss and dysregulation of the complement system is thought to be associated with the disease. To investigate associations of polymorphisms in AMD susceptibility genes with systemic complement activation, 2655 individuals were genotyped for 32 single nucleotide polymorphisms (SNPs) in or near 23 AMD associated risk genes. Component 3 (C3) and its catabolic fragment C3d were measured in serum and AMD staging was performed using multimodal imaging. The C3d/C3 ratio was calculated and associations with environmental factors, SNPs and various haplotypes of complement factor H (CFH) genes and complement factor B (CFB) genes were analyzed. Linear models were built to measure the influence of genetic variants on the C3d/C3 ratio. The study cohort included 1387 patients with AMD and 1268 controls. Higher C3d/C3 ratios were found for current smoker (p = 0.002), higher age (p = 1.56 × 10(-7)), AMD phenotype (p = 1.15 × 10(-11)) and the two SNPs in the C3 gene rs6795735 (p = 0.04) and rs2230199 (p = 0.04). Lower C3d/C3 ratios were found for diabetes (p = 2.87 × 10(-6)), higher body mass index (p = 1.00 × 10(-13)), the SNPs rs1410996 (p = 0.0001), rs800292 (p = 0.003), rs12144939 (p = 4.60 × 10(-6)) in CFH, rs4151667 (p = 1.01 × 10(-5)) in CFB and individual haplotypes in CFH and CFB. The linear model revealed a corrected R-square of 0.063 including age, smoking status, gender, and genetic polymorphisms explaining 6.3% of the C3d/C3 ratio. After adding the AMD status the corrected R-square was 0.067. In conclusion, none of the evaluated genetic polymorphisms showed an association with increased systemic complement activation apart from two SNPs in the C3 gene. Major genetic and non-genetic factors for AMD were not associated with systemic complement activation.http://europepmc.org/articles/PMC3968152?pdf=render |
| spellingShingle | Tina Ristau Constantin Paun Lebriz Ersoy Moritz Hahn Yara Lechanteur Carel Hoyng Eiko K de Jong Mohamed R Daha Bernd Kirchhof Anneke I den Hollander Sascha Fauser Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels. PLoS ONE |
| title | Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels. |
| title_full | Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels. |
| title_fullStr | Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels. |
| title_full_unstemmed | Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels. |
| title_short | Impact of the common genetic associations of age-related macular degeneration upon systemic complement component C3d levels. |
| title_sort | impact of the common genetic associations of age related macular degeneration upon systemic complement component c3d levels |
| url | http://europepmc.org/articles/PMC3968152?pdf=render |
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