title: Variation in complement component C1 inhibitor in age-related macular degeneration.
abstract: This study assessed variation in plasma levels of the complement regulatorC1 inhibitor (C1inh) in patients with age related macular degeneration (AMD) and controls. Plasma from391 AMD cases and 370 controls was assayed by rate nephelometry to determine C1inh protein levels. Protein levels were analysed for relationships with age, gender, smoking, AMD disease status and genetic variation in the SERPING1 gene, which encodes C1inh, using a multivariate analysis. t-Tests show a significant difference in C1inh levels in AMD cases compared with controls (p=2.340E-6), smokers compared to non-smokers (p=1.022E-4) and females compared to males (p=1.661E-7). Multivariate analysis shows that after accounting for gender and smoking AMD status remained significant. Age was included in the model but was not significant. Including genetic variation in the model shows that one significant SNP (rs2649663) 5' of the SERPING1 gene is associated with C1inh levels though this SNP is not associated with AMD. This suggests that genetic variation in the promoter region of the SERPING1 gene may influence expression of the gene.
authors.affiliation: Genetic Epidemiology & Bioinformatics Group, Human Genetics Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton, UK.
authors.forename: J
authors.initials: J
authors.lastname: Gibson
authors.forename: S
authors.initials: S
authors.lastname: Hakobyan
authors.forename: A J
authors.initials: AJ
authors.lastname: Cree
authors.forename: A
authors.initials: A
authors.lastname: Collins
authors.forename: C L
authors.initials: CL
authors.lastname: Harris
authors.forename: S
authors.initials: S
authors.lastname: Ennis
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
authors.forename: A J
authors.initials: AJ
authors.lastname: Lotery
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003172:Complement C1 / Q000037:antagonists & inhibitors; D003174:Complement C1 Inactivator Proteins / Q000235:genetics*; D050718:Complement C1 Inhibitor Protein / Q000032:analysis* / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012737:Sex Factors; D012907:Smoking
chemical_list: D003172:Complement C1; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human