Cholesteryl Ester Transfer Protein Gene Polymorphisms and Longevity Syndrome

Abstract

Purpose:High levels of high density lipoprotein (HDL) cholesterol are associated with a decreased risk of coronary heart disease (CHD). Subjects with high levels of HDL cholesterol (>70 mg/dl; 1.79 mmol/l) as well as high levels of low density lipoprotein (LDL) cholesterol, could represent a group with longevity syndrome (LS). Since HDL particles are influenced by cholesteryl ester transfer protein (CETP) activity, it is worth studying the CETP polymorphism. The aim of the study was to detect whether 2 genetic variants of the CETP are associated with the LS.Subjects and Methods:The study population consisted of 136 unrelated men and women with no personal and family history of CHD; 69 met the criteria for LS and 67 did not meet these criteria and had “normal” HDL cholesterol (>40 and <70 mg/dl; >1.03 and <1.79 mmol/l). All patients were genotyped for the TaqIB and I405V polymorphisms.Results:The B2 allele frequency of TaqIB polymorphism was higher in the LS in comparison with the non-LS group (p=0.03) whereas B1 allele frequency was higher in the non-LS group (p=0.03).Conclusions:Gene polymorphisms could help decide whether individuals who have increased levels of both LDL cholesterol and HDL cholesterol require treatment. Some of the prerequisites could include that subjects with LS should not only have very high levels of HDL cholesterol but also favorable gene polymorphisms. However, further investigations with a larger sample and including other gene polymorphisms, are needed.

Cholesteryl ester transfer protein Taq IB polymorphism and its association with serum lipid levels and longevity in Chinese Bama Zhuang population

“…We also found higher HDL-C and LDL-C levels in the long-lived subjects as compared to general populations. Moreover, this raised HDL-C was associated with B2 allele and B2B2 genotype, which was consistent with some previous reports [12,14,34,44-46], but not others [17,47]. It is widely accepted that B2 allele carriers exhibit lower CETP levels and/or activity, leading to a dysfunction of the reverse cholesterol transport, causing an accumulation of cholesterol ester in HDL style and thus increasing the levels of HDL-C.…”

Ideal lipid profile and genes for an extended life span

“…A meta-analysis of seven studies reported a lower CVD risk in B2 compared with B1 homozygotes [89]. Moreover, our group reported a positive association between B2 allele and individuals with high HDL-C (>70 mg/dl) concentration and exceptional longevity in the family (at least one relative aged >90 years) [44].…”

“…There are more than 100 candidate genes potentially involved in human longevity; in this review the focus will be on genes involved in lipid metabolism. Such genes are apolipoprotein (apo)E [40], adiponectin (ADIPOQ), leptin (LEP) [41], angiotensin-converting enzyme (ACE) [42], angiotensinogen [43], cholesteryl ester transfer protein (CETP) [44], paraoxonase 1 (PON1) [45], and peroxisome proliferatoractivated receptor (PPAR)-g [46]. …”

Phenotypes and Genotypes of High Density Lipoprotein Cholesterol in Exceptional Longevity

“…In addition, a number of studies in European and Chinese populations[42-44] did not find associations between cognition and CETP I405V genotypes and a recent investigation in a cohort of European ancestry actually found the CETP 405VV genotype to be associated with an increased risk of Alzheimer’s disease[45]. It is important to note, though, that these studies differed in methodologies from the previously mentioned ones and that the overall frequency of the CETP VV genotype in the Greek, as well as some of the other European study populations,[41, 45] was very low; thus highlighting the possibility that longevity genotypes may differ between different regions and ethnicities.…”

“…Although larger HDL and LDL particle size has been associated with longevity in the long-living Dutch families, as well as in those surviving to age 90 without a familial history of longevity[7, 39], and the offspring of long-lived siblings had significantly larger lipoprotein particle sizes compared to controls [39], this phenotype was not explained by the CETP 405 VV genotype in these study populations. The frequency distribution of this genotype also did not resemble the longevity genotype in a group of Italian centenarians and middle-aged Greeks with familial longevity[40, 41]. In addition, a number of studies in European and Chinese populations[42-44] did not find associations between cognition and CETP I405V genotypes and a recent investigation in a cohort of European ancestry actually found the CETP 405VV genotype to be associated with an increased risk of Alzheimer’s disease[45].…”