Cholesteryl ester transfer protein and metabolic syndrome
HDL Forum Editor Professor Kerry-Anne Rye discusses findings from a brief report suggesting a potential role for cholesteryl ester transfer protein (CETP) in the metabolic syndrome, published in Obesity.
Sandhofer A, Tatarczyk T, Laimer M et al. The Taq1B variant in the Cholesteryl Ester-Transfer Protein gene and the risk of metabolic syndrome. Obesity 2008;doi:10.1038/oby2007.130.
Dyslipidaemia characterised by low levels of high-density lipoprotein (HDL) cholesterol, elevated triglycerides and an increase in small, dense low-density lipoprotein (LDL) cholesterol, is consistent with metabolic syndrome criteria.
CETP transfers cholesteryl esters and triglycerides between cholesterol-rich lipoproteins and triglyceride-rich lipoproteins (Figure 1). Under circumstances where triglyceride-rich lipoprotein levels are increased, CETP decreases HDL levels and LDL particle size . Genetic variants of the CETP gene influence CETP levels and activity. One of the most studied variants is the CETP Taq1B variant. The B2 allele of this variant is characterised by decreased CETP activity, resulting in an increase in HDL cholesterol levels.
In this report, Sandhofer and colleagues investigated the effect of the Taq1B variant on the risk of metabolic syndrome in 1,503 participants of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n=486) by enzyme-linked immunosorbent assay.
The overall prevalence of metabolic syndrome in this study cohort was 16.7% (13.5% in women and 18.5% in men).
The Taq1B polymorphism significantly influenced CETP levels, HDL levels and LDL particle size (p<0.001) (Table 1).
Table 1. Effect of Taq1B polymorphism on CETP levels, HDL cholesterol and LDL size
| B1B1 | B1B2 | B2B2 | p-value | |
| CETP (μg/mL) | 1.74 ± 0.73 | 1.49 ± 0.64 | 1.37 ± 0.57 | p<0.001 |
| HDL-C (mg/dL) | 58 ± 15 | 60 ± 15 | 63 ± 16 | p<0.001 |
| LDL size (nm) | 26.5 ± 1.1 | 26.7 ± 1.1 | 26.9 ± 1.0 | p<0.001 |
The relative risk of the metabolic syndrome was significantly reduced in carriers of at least one B2 allele by 32% (odds ratio 0.68, 95%CI 0.51-0.89, p=0.005). This relationship was evident even after adjusting for age, sex and individual components of the metabolic syndrome.
The researchers suggested that variation in the CETP gene might be associated with the risk of metabolic syndrome, independently from its individual components, including HDL cholesterol. CETP may have potential novel roles in the development of obesity, a key component of the metabolic syndrome, supported by recent experimental evidence.1 The Taq1B polymorphism of the CETP gene and its effect on HDL levels was first reported in the late 1980’s. Compared to carriers of the less common B2B2 allele, individuals who are homozygous for the B1B1 allele generally have increased CETP expression and reduced HDL levels, WhIle it seems reasonable to expect the changes in HDL levels that are associated with this polymorphism to impact on cholesterol transport, and alter coronary heart disease risk, this appears to be the case only in certain populations. This is almost certainly because many of these studies were conducted in small numbers of subjects and there was wide variation in the end points.
It could be argued that this is also true for the study of Sandhofer et al. In spite of this, their observation that carriers of the Taq1B B2 allele may have a decreased risk of developing the metabolic syndrome is of considerable interest and definitely deserving of further study given the rapid increase in the incidence of this disorder in recent years.
References
1. Izem L, Morton RE. Possible role for intracellular cholesteryl ester transfer protein in adipocyte lipid metabolism and storage. J Biol Chem 2007;282:21856-65.
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