The purpose of this meta-analysis was to detect the association between the cholesteryl ester transfer protein gene polymorphisms and the risk of Alzheimer's disease (AD), carotid atherosclerosis, longevity, and the efficacy of statin therapy. Databases of MEDLINE, EMBASE, BIOSIS, the Cochrane Library, and the Chinese National Knowledge Infrastructure were systematically searched. Thirty-two studies were included in this meta-analysis. There was no difference in the I405V, C629A, and Taq1B polymorphisms between AD and control groups. However, stratified analysis showed that AD group had higher B2B2 genotype frequency than control group in Asian populations with APOE4+ in Taq1B. I405V and Taq1B polymorphisms were not associated with the risk of carotid atherosclerosis and longevity. The efficacy of statin therapy was not associated with Taq1B polymorphism. In conclusion, there was no association between cholesteryl ester transfer protein gene polymorphisms and the risk of AD, carotid atherosclerosis, longevity, and the efficacy of statin therapy in the pooled effects of overall population. However, the B2B2 genotype of Taq1B was associated with increased risk of AD in the Asian populations with APOE4+.
Alzheimer's disease (AD), carotid atherosclerosis, and dyslipidemia result in diminished quality of life, life-years lost, and enormous medical costs. Therefore, it is necessary to detect the association of genetic variants and these diseases.
Recently, the association of cholesteryl ester transfer protein (CETP) gene and dyslipidemia, the risk of AD, carotid atherosclerosis, longevity, or the efficacy of statin therapy has been widely reported (Agerholm-Larsen et al., 2000, Al-Daghri et al., 2003, Bauerfeind et al., 2002, Bercovich et al., 2006, Fiegenbaum et al., 2005, Murphy et al., 2012, Parra et al., 2012, Qureischie et al., 2009, Soyal et al., 2011, Winkelmann et al., 2003 and Yu et al., 2012). Plasma CETP is an extremely hydrophobic glycoprotein with a relative molecular mass of 74,000, and consists of 476 amino acids with 4 N-linked glycosylation sites. The human CETP spans approximately 25 kb, encompasses 16 exons, and is found on chromosome 16q13. Several polymorphisms have been identified in the human CETP ( Corbex et al., 2000). CETP regulates cholesterol homeostasis via the transfer of cholesteryl esters from high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) in exchange for triacylglycerol (TG) ( Barter and Kastelein, 2006). Several single-nucleotide polymorphisms within CETP have been suggested to influence enzymatic activity or gene expression level. In particular, Taq1B (rs708272) is characterized by a silent base change affecting the 277th nucleotide in intron 1 of the gene and possesses a restriction site for the endonuclease Taq1. Mutant alleles of the polymorphism in the Taq1B intron 1 in the CETP have been associated with increased HDL-C concentrations ( Fidani et al., 2004). The I405V (rs5882) located in exon 14 of the CETP is characterized by alteration in the primary structure of the protein. This polymorphism has been related to plasma CETP concentration and HDL-C concentrations and to the degree of carotid atherosclerosis ( Kakko et al., 2000). C629A (rs1800775) within the gene promoter is associated with decreased expression ( Dachet et al., 2000).
Many studies have proved that dyslipidemia is correlated to the risk of AD, carotid atherosclerosis, and longevity, such as a low concentration of HDL-C have been associated with the risk of AD (Brewer, 2004), carotid atherosclerosis (Soyal et al., 2011), and longevity (Kolovou et al., 2010).
It is well established that the risk of AD is dependent on APOE genotype and the ε4 allele of APOE (APOE4+) may be related to AD ( Bertram et al., 2007). However, there probably are several other genes that increase the susceptibility for AD. Recent studies of the link between CETP polymorphisms and the susceptibility of AD, carotid atherosclerosis, longevity, or the efficacy of statin therapy have been published, respectively, but the results are equivocal ( Arai et al., 2003, Arias-Vasquez et al., 2007, Cellini et al., 2005, Chen et al., 2008, Fidani et al., 2004, Kakko et al., 2000, Kuivenhoven et al., 1998, Rodriguez et al., 2006, Soyal et al., 2011, Winkelmann et al., 2003 and Zhu et al., 2005). In many of these studies, the sample sizes were relatively small. Therefore, we performed a meta-analysis of the published studies to derive a more precise estimation of the association.
