Complement component 3: an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish cohort.
OBJECTIVE
A non-synonymous single nucleotide polymorphism (SNP) in complement component 3 has been shown to increase the risk of age-related macular degeneration (AMD). We assess its effect on AMD risk in a Northern Irish sample, test for gene-gene and gene-environment interaction, and review a risk prediction model.


METHODS
SNP rs2230199 was genotyped in 1,358 samples, which comprised 437 cases, 436 no-disease controls, and 485 participants randomly sampled from the Northern Ireland population. Allele frequencies were assessed in cases and controls. Logistic regression analysis was used to assess interaction and develop a risk prediction model.


RESULTS
We report a minor allele frequency of 0.248 for rs2230199 in the population (n=485), 0.296 in cases (n=437), and 0.221 in controls (n=436; odds ratio [OR]=1.48; confidence interval [CI]: 1.19-1.85; p=0.0003). The significant association is retained following multivariate analysis with adjustment for age, smoking status, Complement Factor H (CFH), Age-Related Maculopathy Susceptibility 2 (ARMS2), Complement Component 2 (CC2), and Complement Factor B (CFB; OR=1.45; CI: 1.10-1.91; p=0.009). No evidence to support an interaction between any of the covariates within the regression model was found. The area under the receiver operator characteristic curve calculated for the fully adjusted model, including all variables, was 0.86 for late AMD.


CONCLUSIONS
Our study confirmed the association between Complement Component 3 (C3) and late-stage AMD. There was no evidence for an interaction with environmental exposures, nor did we find data to support a gene-gene effect.
McKay
Gareth J
GJ
Centre for Vision and Vascular Sciences, Queen's University of Belfast, Belfast, Northern Ireland BT12 6BA, UK. g.j.mckay@qub.ac.uk
Dasari
Shilpa
S
Patterson
Christopher C
CC
Chakravarthy
Usha
U
Silvestri
Giuliana
G
D000368:Aged; D015331:Cohort Studies; D003176:Complement C3 / Q000235:genetics*; D016001:Confidence Intervals; D004777:Environment; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007494:Ireland; D016015:Logistic Models; D008268:Macular Degeneration / Q000235:genetics*; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D012372:ROC Curve
D003176:Complement C3