Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

To explore the association between polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of complement factor H (CFH) Y402H, LOC387715 A69S and smoking.Pooled data from the prospective, population-based Rotterdam Study (enrolment between 1990 and 1993, and 3 follow-up examinations between September 1, 1993, and December 31, 2004) and an independent case-control study from the Netherlands.The Rotterdam Study comprised a total of 6418 persons aged >or=55 years who had gradable fundus photographs. The case-control study consisted of 357 unrelated AMD patients and 173 control individuals aged >or=55 years.The variants R102G and P314L of the C3 gene, CFH Y402H and LOC387715 A69S, were genotyped in all study participants. Information on cigarette smoking was obtained by interview at baseline.Early and late stages of prevalent and incident AMD, graded according to the international classification and grading system for AMD.We found a population frequency of 0.217 for R102G and 0.211 for P314L in the Rotterdam Study. Both alleles significantly increased the risk of early AMD and all subtypes of late AMD, and this risk seemed to be independent of CFH Y402H, LOC387715 A69S, and smoking. Detailed analysis showed that the haplotype carrying both alleles had the highest frequency difference between cases and controls (P=0.006). We estimated a total population-attributable risk of 14.6%. A meta-analysis of all currently available data yielded a pooled odds ratio (OR) of 1.61 (95% confidence interval [CI], 1.46-1.78) for the R102G allele, and an OR of 1.50 (95% CI, 1.31-1.71) for the P314L allele.Our study showed a significant association between variants in the C3 gene and AMD and further highlights the crucial role of the complement pathway in the etiology of AMD.

Original publication

DOI

10.1016/j.ophtha.2008.09.055

Type

Journal article

Journal

Ophthalmology

Publication Date

03/2009

Volume

116

Pages

474 - 480.e2

Addresses

Department of Epidemiology and Biostatistics, Rotterdam, Erasmus Medical Centre, the Netherlands.

Keywords

Humans, Macular Degeneration, Proteins, Complement Factor H, Chromatography, High Pressure Liquid, Risk Factors, Case-Control Studies, Follow-Up Studies, Prospective Studies, Smoking, Genotype, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Complement C3, Female, Male