Association Study On The CETP TaqIB And1405V Polymorphisms With Lipids And Longevity In Guangxi Hongshuihe River Basin

Background:Cholesteryl ester transfer protein (CETP), an important regulating protein in lipid metabolism, plays key role in the reverse transportation of cholesterol. CETP is one of the most important determinants for plasma HDL-C level. Any variant in CETP gene may change the level of HDL-C, influence the particle size and serum concentration of HDL-C and LDL-C as well as lipid metabolism, increase the risk of cardiovascular disease, and then impact the survival of individual. Some studies have been conducted on the relationship between CETP polymorphism and human longevity, but no concordant conclusion has been established.Objectives:The aims of the current study are to explore the polymorphisms of CETP Taq IB and1405V in the long-living population residing Guangxi Hongshuihe River basin and explore the possible association with lipid level and human longevity in the region.Methods:Genotyping of CETP Taq IB and I405V was performed with PCR-RFLP for523Zhuang long-living cohort (long-living group, LG) and498ethnic-matched controls (non-long-living group, non-LG) living in Hongshuihe River basin. Association analyses were conducted among genotypes and blood pressure, body mass index (BMI), total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C).Results:1. General clinical characteristics and lipid levels:Blood pressure level, hypertension rate, TC, HDL-C and LDL-C were significantly higher, while BMI, TG level and the rate of dyslipidemia were significantly lower in LG than in non-LG.2. Genotypes:The dominant allele and genotypes of CETP Taq IB and1405V are B1(>60%), B1B1, B1B2and Ⅰ (about58%), Ⅱ, Ⅳ, respectively. No significantly different allelic and genotypic frequency on CETP Taq IB and I405V loci was found between the two groups. However, when stratified by gender, females in the non-LG were found to carry more Taq IB B2than did LG (33.3%vs39.1%, P<0.05); remarkable divergence was observed in the genotype frequencies between the two genders (P=0.008) on I405V locus in the non-LG, with females carrying more Ⅴ Ⅴ, Ⅱ and less Ⅳ than did males (20.4vs12.6, 37.6vs32.4, and42.0vs54.9, respectively.).3. Relationship between genotypes and BMI:Individuals studied were classified into two subgroups:normal weight (BMI<24kg/m2) and overweight (BMI≥24kg/m2). The rate of overweight in non-LG was dramatically higher than in LG (24.1%vs12.4%, P<0.05). No difference of genotypic and allelic frequency was found between overweight and non-overweight on Taq IB locus. However, the frequency of VV and Ⅱ was found higher while IV was lower in the overweight subgroup than that in the non-overweight (P=0.011).4. Relationship between genotypes and lipid levels:Intra-group comparisons showed that the HDL-C levels of B2B2and B1B2carriers were significantly higher than B1B1carriers in both LG and non-LG, while HDL-C of B1B1carriers and LDL-C of all genotypes in LG were significantly higher than were non-LG (P<0.05, for all) when inter-group comparisons were done. The significance remained in the males in LG after stratified by sex. On1405V locus, no difference was revealed among genotypes in both LG and non-LG, however, male’s TC and LDL-C levels of Ⅱ carriers in non-LG tended to be higher than that of Ⅳ and VV carriers.5. Linear regressive analysis:In the overall populations studied, levels of TC and TG were positively associated with diastolic pressure and BMI (P<0.05, for all) whereas were inversely related with age (P<0.01～0.05); HDL-C level was positively associated with age and Taq IB genotypes (P<0.01) and negatively associated with BMI and1405V genotypes (P<0.01～0.05); LDL-C level was positively associated with diastolic pressure (P<0.01).Conclusions:1. There are significant divergence on the lipid profiles, dyslipidemia rate, hypertension rate between the long-living cohort and general population in Guangxi Hongshuihe river basin.2. Overall, there are no differences on the distribution of allelic and genotypic frequencies of CETP Taq IB and1405Ⅴ.3. CETP IB B2carriers, including B2B2and B1B2genotypes, tend to have more advantages in dealing with cholesterol, with presenting higher HDL-C levels which are favorable in the preventing the development of cardiovascular disease (CVD).4. The longevity in Guangxi Hongshuihe region has relationship with CETP polymorphisms to some extent which is not independent of sex. Some favorable genotypes may influence the lipid levels, HDL-C in particular, reduce the risks of aged related diseases such as CHD, and ultimately contribute to the longevity in the region.