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

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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
Volume17
Issue number9
DOIs
StatePublished - May 1 2008

Fingerprint

Complement Factor H
Chlamydophila pneumoniae
Gene-Environment Interaction
Macular Degeneration
Smoking
Odds Ratio
Confidence Intervals
Infection
Genes
Disease Progression
Bacterial Antibodies
Alleles
Antibodies
Genotype
DNA

Cite this

Baird, P. N., Robman, L. D., Richardson, A. J., Dimitrov, P. N., Tikellis, G., Mccarty, C. A., & Guymer, R. H. (2008). Gene-environment interaction in progression of AMD: The CFH gene, smoking and exposure to chronic infection. Human molecular genetics, 17(9), 1299-1305. https://doi.org/10.1093/hmg/ddn018

Gene-environment interaction in progression of AMD : The CFH gene, smoking and exposure to chronic infection. / Baird, Paul N.; Robman, Luba D.; Richardson, Andrea J.; Dimitrov, Peter N.; Tikellis, Gabriella; Mccarty, Catherine A.; Guymer, Robyn H.

In: Human molecular genetics, Vol. 17, No. 9, 01.05.2008, p. 1299-1305.

Research output: Contribution to journalArticle

Baird, PN, Robman, LD, Richardson, AJ, Dimitrov, PN, Tikellis, G, Mccarty, CA & Guymer, RH 2008, 'Gene-environment interaction in progression of AMD: The CFH gene, smoking and exposure to chronic infection', Human molecular genetics, vol. 17, no. 9, pp. 1299-1305. https://doi.org/10.1093/hmg/ddn018
Baird PN, Robman LD, Richardson AJ, Dimitrov PN, Tikellis G, Mccarty CA et al. Gene-environment interaction in progression of AMD: The CFH gene, smoking and exposure to chronic infection. Human molecular genetics. 2008 May 1;17(9):1299-1305. https://doi.org/10.1093/hmg/ddn018
Baird, Paul N. ; Robman, Luba D. ; Richardson, Andrea J. ; Dimitrov, Peter N. ; Tikellis, Gabriella ; Mccarty, Catherine A. ; Guymer, Robyn H. / Gene-environment interaction in progression of AMD : The CFH gene, smoking and exposure to chronic infection. In: Human molecular genetics. 2008 ; Vol. 17, No. 9. pp. 1299-1305.
@article{1167b7d56e38420d9d0654b7100e51c9,
title = "Gene-environment interaction in progression of AMD: The CFH gene, smoking and exposure to chronic infection",
abstract = "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.",
author = "Baird, {Paul N.} and Robman, {Luba D.} and Richardson, {Andrea J.} and Dimitrov, {Peter N.} and Gabriella Tikellis and Mccarty, {Catherine A.} and Guymer, {Robyn H.}",
year = "2008",
month = "5",
day = "1",
doi = "10.1093/hmg/ddn018",
language = "English (US)",
volume = "17",
pages = "1299--1305",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Gene-environment interaction in progression of AMD

T2 - The CFH gene, smoking and exposure to chronic infection

AU - Baird, Paul N.

AU - Robman, Luba D.

AU - Richardson, Andrea J.

AU - Dimitrov, Peter N.

AU - Tikellis, Gabriella

AU - Mccarty, Catherine A.

AU - Guymer, Robyn H.

PY - 2008/5/1

Y1 - 2008/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=42449092918&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42449092918&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddn018

DO - 10.1093/hmg/ddn018

M3 - Article

C2 - 18203751

AN - SCOPUS:42449092918

VL - 17

SP - 1299

EP - 1305

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 9

ER -