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Cet abstract a été assigné à session BOG-SBO: Medisch netvlies/ Rétine médicale
TitreComplement factor H polymorphism, inflammation, haplotypes of C-reactive protein and age-related macular degeneration in the general population
Abstract Nr.247
ButAge-related macular degeneration (AMD) is the leading cause of visual impairment in the elderly. Case-control studies reported an association between the gene for complement factor H (CFH), a regulator of complement, and AMD. We assessed the relevance of CFH for the general population, and investigated potentially modifying factors.
MéthodesWe determined the Y402H allele of CFH in 5681 participants of the population-based Rotterdam Study, assessed early and late AMD at baseline and during 7.6 years follow-up, and calculated risks of AMD. We then related these risks to serum markers of inflammation, smoking, and genetic variation of C-reactive protein (CRP).
RésultatsThe frequency of the Y402H allele was 36.2%. The risk of AMD increased in an allele-dosed manner with clinical severity with an odds ratio (OR) for early AMD of 2.71 (95% CI 2.10, 3.50), and for late AMD of 11.02 (6.82, 11.81) for homozygous subjects. Absolute risks of late AMD by 95 years were 89.4% for homozygous, 76.2% for heterozygous, and 30.6% for wild-type genotypes. The population attributable risk of Y402H was 54.0%. Elevated erythrocyte sedimentation rates further increased risks with OR 20.2 (95% CI 9.5, 43.0), elevated serum CRP with OR 25.6 (9.8, 67.0), and smoking with OR 34.0 (13.0, 88.6) for homozygous persons compared to wild-types without these determinants. CRP haplotypes conferring high CRP levels significantly influenced the effect of CFH (P<0.008).
ConclusionThis CFH polymorphism accounts for the majority of AMD in the general population, and is particularly perilous in the presence of environmental and genetic stimulators of the complement cascade.
Auteur 1
NomDESPRIET
InitialesDDG
InstitutErasmus Medical Center
VilleRotterdam
Auteur 2
NomKLAVER
InitialesCCW
InstitutErasmus Medical Center
VilleRotterdam
Auteur 3
NomBERGEN
InitialesAAB
InstitutAMC
VilleAmsterdam
Auteur 4
NomHOFMAN
InitialesA
InstitutErasmus Medical Center
VilleRotterdam
Auteur 5
NomUITTERLINDEN
InitialesAG
InstitutErasmus Medical Center
VilleRotterdam
Auteur 6
Nomvan DUIJN
InitialesCM
InstitutErasmus Medical Center
VilleRotterdam
Auteur 7
Nomde JONG
InitialesPTVM
InstitutErasmus Medical Center
VilleRotterdam
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