Complement Component 3; an assessment of association with AMD and analysis of gene-gene and gene-environment interactions in a Northern Irish Cohort

[摘要] Purpose: A non-synonymous singlenucleotide polymorphism (SNP) in complement component 3 has been shownto increase the risk of age-related macular degeneration (AMD). Weassess its effect on AMD risk in a Northern Irish sample, test forgene–gene and gene–environment interaction, and review a riskprediction model. Methods: SNP rs2230199was genotyped in 1,358 samples, which comprised 437 cases, 436no-disease controls, and 485 participants randomly sampled from theNorthern Ireland population. Allele frequencies were assessed in casesand controls. Logistic regression analysis was used to assessinteraction and develop a risk prediction model. Results: We report a minor allelefrequency of 0.248 for rs2230199 inthe 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 followingmultivariate analysis with adjustment for age, smoking status,Complement Factor H (CFH), Age-Related MaculopathySusceptibility 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 covariateswithin the regression model was found. The area under the receiveroperator characteristic curve calculated for the fully adjusted model,including all variables, was 0.86 for late AMD. Conclusions: Our study confirmed theassociation between Complement Component 3 (C3) and late-stageAMD. There was no evidence for an interaction with environmentalexposures, nor did we find data to support a gene–gene effect.

[学科分类] 生物化学/生物物理