Gene–environment interaction in progression of AMD: the CFH gene, smoking and exposure to chronic infection

• Published in: Human molecular genetics Vol. 17; no. 9; pp. 1299 - 1305
• Main Authors: Baird, Paul N., Robman, Luba D., Richardson, Andrea J., Dimitrov, Peter N., Tikellis, Gabriella, McCarty, Catherine A., Guymer, Robyn H.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.05.2008; Oxford Publishing Limited (England)
• Subjects: Age Factors; Aged; Aged, 80 and over; Alleles; Antibodies, Bacterial - immunology; Australia - epidemiology; Biological and medical sciences; Chlamydophila Infections - epidemiology; Chlamydophila Infections - immunology; Chlamydophila Infections - microbiology; Chlamydophila pneumoniae; Chlamydophila pneumoniae - immunology; Cohort Studies; Complement Factor H - genetics; Disease Progression; Female; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Humans; Immunoglobulin G - immunology; Logistic Models; Macular Degeneration - epidemiology; Macular Degeneration - genetics; Macular Degeneration - pathology; Male; Medical sciences; Middle Aged; Molecular and cellular biology; Polymorphism, Single Nucleotide; Risk Factors; Smoking; Tobacco, tobacco smoking; Toxicology; Australia; Infection; Chronic; Gene; Gene interaction; Tobacco smoking; Environment; Genetics; Exposure
• ISSN: 0964-6906; 1460-2083
• DOI: 10.1093/hmg/ddn018

A number of risk factors including the complement factor H (CFH) gene, smoking and Chlamydia pneumoniae have been associated with age-related macular degeneration (AMD). However, the mechanisms underlying how these risk factors might be involved in disease progression and disease aetiology is poorly understood. A cohort series of 233 individuals followed for AMD progression over a mean period of 7 years underwent a full eye examination, blood was taken for DNA and antibody titre and individuals completed a standard medical and general questionnaire. Y402H variants of the CFH gene were assessed with disease progression as well as examination of interaction between Y402H variants and smoking and Y402H variants and the pathogen C. pneumoniae. The CC risk genotype of Y402H was significantly associated with increased AMD progression [odds ratio (OR) 2.43, 95% confidence interval (95% CI) 1.07–5.49] as was smoking (OR 2.28, 95% CI 1.26–4.12). However, the risk of progression was greatly increased to almost 12-fold (OR 11.8, 95% CI 2.1–65.8) when, in addition to having the C risk allele, subjects also presented with the upper tertile of antibodies to the bacterial pathogen C. pneumoniae compared with those with the T allele of Y402H and the lowest antibody tertile. This demonstrates for the first time the existence of a gene environment–interaction between pathogenic load of C. pneumoniae and the CFH gene in the aetiology of AMD.