Polymorphisms and haplotypes in the C-reactive protein gene and risk of dementia.
OBJECTIVE
Inflammation plays a role in the pathogenesis of dementia and Alzheimer's disease (AD). Studies examining serum levels of C-reactive protein in relation to dementia yielded conflicting results. Since serum levels of C-reactive protein are partly determined by genetic factors, we examined the association between genetic variation in the C-reactive protein gene with dementia and AD.


METHODS
This study was performed in the Rotterdam Study, a population-based prospective cohort study among elderly. Polymorphisms in the C-reactive protein gene (1184C>T, 2042C>T and 2911C>G) tagging the common haplotypes were genotyped and haplotypes were constructed. During follow-up (mean 9.2 years) 607 dementia cases were identified. We estimated the association between polymorphisms and haplotypes with dementia and AD with Cox' proportional hazard models.


RESULTS
The T allele of the C-reactive protein 2042C>T polymorphism, related to lower serum levels of C-reactive protein, was associated with a lower risk of dementia and AD. This association was strongest in APOE epsilon4 allele carriers.


CONCLUSIONS
These findings suggest that C-reactive protein plays a role in development of dementia.
van Oijen
Marieke
M
Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
de Maat
Moniek P M
MP
Kardys
Isabella
I
de Jong
Frank Jan
FJ
Hofman
Albert
A
Koudstaal
Peter J
PJ
Witteman
Jacqueline C
JC
Breteler
Monique M B
MM
D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D002097:C-Reactive Protein / Q000235:genetics*; D015331:Cohort Studies; D003704:Dementia / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk
D001057:Apolipoproteins E; D002097:C-Reactive Protein