Polymorphisms and haplotypes in the C-reactive protein gene and risk of dementia

van Oijen, Marieke; de Maat, Moniek P.M.; Kardys, Isabella; de Jong, Frank Jan; Hofman, Albert; Koudstaal, Peter J.; Witteman, Jacqueline C.; Breteler, Monique M.B.

doi:10.1016/j.neurobiolaging.2006.06.015

« Previous Next »Neurobiology of Aging
Volume 28, Issue 9 , Pages 1361-1366, September 2007

Polymorphisms and haplotypes in the C-reactive protein gene and risk of dementia

Marieke van Oijen
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
- Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
Moniek P.M. de Maat
- Department of Hematology, Erasmus Medical Center, Rotterdam, The Netherlands
Isabella Kardys
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Frank Jan de Jong
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
- Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
Albert Hofman
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Peter J. Koudstaal
- Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
Jacqueline C. Witteman
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Monique M.B. Breteler
- Department of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
- Corresponding author. Tel.: +31 10 4087489; fax: +31 10 4089382.

Received 14 February 2006; received in revised form 9 June 2006; accepted 19 June 2006. published online 20 July 2006.

Abstract

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 ɛ4 allele carriers.