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

Paul N. Baird, Luba D. Robman, Andrea J. Richardson, Peter N. Dimitrov, Gabriella Tikellis, Catherine A. Mccarty, Robyn H. Guymer

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67 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1299-1305
Number of pages7
JournalHuman molecular genetics
Issue number9
StatePublished - May 1 2008

Bibliographical note

Funding Information:
This project was supported by the National Health and Medical Research Council of Australia through a Clinical Fellowship to R.H.G. and NHMRC grant 128201, the JACOM Foundation, the Ophthalmic Research Institute of Australia, Perpetual Trustees Australia Ltd (Ramaciotti Foundation), ANZ Executors & Trustee Company Ltd (The Hugh D.T. Williamson Foundation under the Medical Research and Technology in Victoria Program), The Royal Victorian Institute for the Blind, The Royal Victorian Eye and Ear Hospital Research Committee, The Lions Club of Victoria and The Australian Institute of Health and Welfare.

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