Cholesterol plays an essential physiological role in humans. It is mainly synthesized and esterified by the liver and then is secreted from the liver into plasma as very low density lipoprotein (VLDL), which gets converted to low density lipoprotein (LDL). In contrast, reverse cholesterol transport (RCT) mediates the conveyance of free unesterified cholesterol mobilized from peripheral cells and destined for disposal by the liver. In this process, cholesteryl ester transfer protein (CETP), a 74-kDa hydrophobic glycoprotein, facilitates the transfer of cholesterol ester from high density lipoprotein (HDL) to apolipoprotein (Apo) B-containing lipoproteins including VLDL and LDL, for disposal via the LDL receptor pathway in the liver, and of triglyceride (TG) in the opposite direction in plasma [1, 2]. Remarkably, these rationales indicate that CETP plays a significant role in the modulation of cholesterol.
In humans, CETP is expressed predominantly in the liver, spleen, and adipose tissue . Detectable levels of CETP can also be seen in the small intestine, adrenal glands, heart, kidneys, or skeletal muscle . The gene encoding CETP consists of 16 exons and 15 introns encompassing 25 kb on chromosome 16q12-21 adjacent to the lecithin-cholesterol acyltransferase gene . To date, a number of common polymorphisms and rare variants at the CETP gene locus, such as I405V, D442G, I14A, A373P, R451Q, promoter polymorphism (Y629A/C, Y1337C/T and Y971G/A), which cause depletion of CETP activity and consequently high high-density lipoprotein cholesterol (HDL-C) in plasma, have been described across populations [5–8]. One of these common polymorphisms is Taq IB, a silent base change affecting the 277th nucleotide in the first intron of the CETP gene . The B2 allele, absence of the Taq I restriction site, has been found to be associated with elevated plasma HDL-C level and reduced plasma CETP mass and activity and coronary heart disease (CHD) risk [9–12], and accordingly to be associated with longer life expectancy [13, 14]. This hypothesis is further supported by the fact that high HDL-C levels are often observed in healthy elderly aged 85 and above [13, 15]. However, inconsistent findings also arose in different studies, e.g., a positive association of HDL-C levels with increased CHD risk has been reported ; not all CETP deficiencies with high HDL-C levels are correlated with longevity . These controversial results suggest that the roles of CETP gene variations in longevity appear much more complex than expected and need further elucidation.
Bama is a remote and mountainous county located in the northwest of Guangxi, People's Republic of China. It has been well known for its longevity for centuries. The population size and centenarian rate in Bama County are around 240,000 and 30/100,000 respectively, according to the National Population Census of China in the past decades [18, 19]. Although a number of studies involving natural environment, dietary habit, socioeconomic status and genetic background have been conducted for decades [19–22], the underlying mechanisms of the longevity in this county are still unknown. Genetically, the majority (> 85%) of the inhabitants living in Bama County belong to the north branch of Zhuang ethnic group. Zhuang is the largest minority in China with a total population of 15 millions [23, 24]. Long-term geographic and social isolation as well as inbreeding result in both cultural and genetic homogeneity of Bama Zhuang branch, and therefore Bama Zhuang has become a useful subgroup for population genetic studies. We have initiated the Bama Longevity Genetic Study (BLGS) since late 1998. Several genetic polymorphisms such as human leukocyte antigen (HLA), ApoE, p53, and transforming growth factor-β1 (TGF-β1) genes and the haplotypes of mitochondria DNA [19, 25–29] have been shown difference between long-lived group (LG) and non-long-lived group (non-LG), indicating that Bama long-lived individuals may have favorable genetic background for their survivals. Therefore, the aim of the present study was to determine the Taq IB polymorphism of CETP gene and its association with serum lipid levels and longevity in the Chinese Bama Zhuang population.