Complement C3 Variant and the Risk of Age-Related Macular Degeneration
| Autor: | D A Thurlby, E Redmond, Humma Shahid, Baljean Dhillon, Anthony T. Moore, Caroline Hayward, Baljinder K Matharu, David Clayton, Ana Maria Armbrecht, Ian J. Deary, T. Sepp, Joanne E. Morgan, Jane C. Khan, John R.W. Yates, Alan C. Bird, Alan F. Wright |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Pathology medicine.medical_specialty Genotype genetic structures Single-nucleotide polymorphism Polymorphism Single Nucleotide Macular Degeneration Membranoproliferative glomerulonephritis Odds Ratio medicine Humans Genetic Predisposition to Disease Protein Structure Quaternary Aged Complement component 5 business.industry Case-control study Complement C5 Complement C3 General Medicine Odds ratio Macular degeneration medicine.disease eye diseases Complement system Logistic Models Case-Control Studies Immunology Female business Retinopathy |
| Zdroj: | New England Journal of Medicine. 357:553-561 |
| ISSN: | 1533-4406 0028-4793 |
| Popis: | Age-related macular degeneration is the most common cause of blindness in Western populations. Susceptibility is influenced by age and by genetic and environmental factors. Complement activation is implicated in the pathogenesis.We tested for an association between age-related macular degeneration and 13 single-nucleotide polymorphisms (SNPs) spanning the complement genes C3 and C5 in case subjects and control subjects from the southeastern region of England. All subjects were examined by an ophthalmologist and had independent grading of fundus photographs to confirm their disease status. To test for replication of the most significant findings, we genotyped a set of Scottish cases and controls.The common functional polymorphism rs2230199 (Arg80Gly) in the C3 gene, corresponding to the electrophoretic variants C3S (slow) and C3F (fast), was strongly associated with age-related macular degeneration in both the English group (603 cases and 350 controls, P=5.9x10(-5)) and the Scottish group (244 cases and 351 controls, P=5.0x10(-5)). The odds ratio for age-related macular degeneration in C3 S/F heterozygotes as compared with S/S homozygotes was 1.7 (95% confidence interval [CI], 1.3 to 2.1); for F/F homozygotes, the odds ratio was 2.6 (95% CI, 1.6 to 4.1). The estimated population attributable risk for C3F was 22%.Complement C3 is important in the pathogenesis of age-related macular degeneration. This finding further underscores the influence of the complement pathway in the pathogenesis of this disease. |
| Databáze: | OpenAIRE |
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