Genetics
A CETP variant raises vascular dementia risk and lowers white matter lesion load, but only in APOE4 non-carriers (J Neural Transm 2009)
Original title: Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions
Researchers investigated whether two putative functional CETP polymorphisms, C-629A and I405V, were associated with vascular dementia risk and whether this depended on APOE4 carrier status, in 163 vascular dementia patients and 452 cognitively healthy controls. Neither polymorphism was associated with vascular dementia risk in the whole sample, but in APOE4 non-carriers, homozygous carriers of the CETP C-629A A allele had increased vascular dementia risk (P equals 0.01), an association not seen in APOE4 carriers. Carriers of the CETP C-629A AA genotype also had decreased frontal white matter lesion load (P equals 0.009), suggesting CETP gene polymorphisms may influence white matter lesion burden and vascular dementia risk specifically in the absence of APOE4.
Original abstract
Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 +/- 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 +/- 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.