Table 3

Comparisons of parameters between subjects with risk/reference alleles in oldest-old females.

APOE*4-carrier APOE*2-carrier CETP*V-carrier CETP*I-carrier P P APOE CETP Number 52 74 244 298 FPG (mmol/L) 5.98 ± 1.58 5.80 ± 1.47 5.73 ± 1.41 5.67 ± 1.49 0.525 0.642 TC (mmol/L) 5.22 ± 1.54 4.52 ± 0.78 4.81 ± 1.09 4.84 ± 1.13 0.004 0.863 TG(mmol/L) 1.75 ± 1.11 1.44 ± 0.78 1.54 ± 0.86 1.34 ± 0.69 0.044 0.003 HDL-c (mmol/L) 1.20 ± 0.26 1.23 ± 0.37 1.25 ± 0.34 1.25 ± 0.37 0.636 0.961 LDL-c (mmol/L) 3.30 ± 1.40 2.70 ± 0.79 2.94 ± 0.99 3.00 ± 1.00 0.007 0.472 BMI (kg/m2) 19.88 ± 3.04 18.92 ± 3.46 18.79 ± 3.39 18.25 ± 3.48 0.115 0.074 HR (times/min) 81.77 ± 14.23 79.86 ± 10.98 79.78 ± 10.82 80.47 ± 12.67 0.398 0.493 SBP (mmHg) 157.45 ± 23.16 154.47 ± 26.36 153.78 ± 25.84 156.90 ± 26.35 0.549 0.232 DBP (mmHg) 83.59 ± 12.60 79.27 ± 12.64 82.44 ± 15.49 82.46 ± 14.86 0.087 0.987

FPG:fasting plasma glucose; TC: total cholesterol; TG: triglycerides; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoproteincholesterol; BMI:bodymass index;HR: heart rate; SBP: systolic blood pressure; DBP: diastolic blood pressure.

subjects to reduce the confounding of gender and ensure a preferable statistical power.

Table 4

OR and 95%CI of hTG by CETP and APOE polymorphism for oldest-old females.

hTG,OR(95%CI) Cases/participants Model 1 Model 2 a CETP*V VV 32/74 2.989 3.264 (1.592–5.612) (1.667–6.392) VI 47/170 1.499 1.335 (0.868–2.588) (0.746–2.389) II 26/128 1.0 (reference) 1.0 (reference) P 0.003 0.001 for trend APOE*4 ε2ε4 + ε3ε4 + ε4ε4 20/52 1.728 1.346 (0.938–3.184) (0.713–2.540) ε2ε2 + ε2ε3 + ε3ε3 85/320 1.0 (reference) 1.0 (reference) P 0.079 0.360 t-test CETP/APOE combination VV/APOE*4 10/12 19.091 7.849 (3.897–93.532) (1.473–41.818) VI/APOE*4 6/18 1.909 1.107 (0.644–5.659) (0.328–3.735) II/non-APOE*4 22/106 1.0 (reference) 1.0 (reference) P 0.001 0.042 for trend

phisms in CETP and APOE might be associated with dyslipidemia in oldest-old Chinese women. First, this was especially pertinent since CETP and APOE are functionally related in the maintenance of circulat- ing lipid homeostasis in animal models and middle-aged populations. Second, CETP*405 V was associated with lower CETP protein serum level and activity and corresponding increase in HDL levels and particle sizes (Sanders et al., 2010; Thompson et al., 2008). Further, APOE*4 was associated with increased TC and LDL-c levels (Bennet et al., 2007). Therefore, their impacts on human lifespan and longevity were tested in many populations, although the results were inconsistent. Third, our recent pilot study identified lower TG and higher LDL-c levels in oldest-old Chinese compared to controls. The difference of genetic contribution for longevity among populations possibly depends on the specific pattern of serum lipids in the longevity group. Accordingly, we focused on the contribution of CETP*405 V and APOE*4 on longevity and dyslipidemia, including hTG in the oldest-old population.

In this study, except for the increased blood pressure, which might be partly influenced by the decline of vascular elasticity, we observed lower TG levels and less frequent obesity in oldest-old females com- pared to controls, suggesting that the general health status of oldest- old females was comparative to controls. Upon analysis of genotype of CETP I405V and APOE, we only found that APOE*4 increased the risk against longevity. However, concerning the contribution for dyslipid- emia in the oldest-old subjects, in addition to the observation that APOE*4 was associated with risk for hTC and mixed dyslipidemia (mixed-dys) as expected, additive model indicated that CETP*V signifi- cantly associated with hTG. Furthermore, the risk for hTG increased with increasing of CETP*V numbers with or without adjustment for age and BMI. Subjects who carry the risk CETP*V had significant higher risk for hTG compared to CETP*II homozygotes independent from APOE*4, age, BMI, alcohol drinking, TC, TG, HDL-c, and LDL-c. Consistent

a Model 2 was adjusted for age and BMI.

4. Discussion

The recent increase in aging worldwide has drawn an ed focus on human healthy longevity by researchers and the public (Dupre et al., 2008). Dyslipidemia has consistently been to be a significant risk factor for CVD and shorten life expectancy US life tables (Stamler et al., 2000). Because of the gender of longevity subjects in our study andphysiological differences genders, and because the effects of APOE polymorphism were to be stronger in women (Song et al., 2004), we only included

Parameters P OR (95% CI) logistic BMI <0.001 1.17 (1.09, 1.26) alcohol drinking 0.049 1.86 (1.00, 3.45) age 0.548 0.98 (0.92, 1.04) TC <0.001 1.50 (1.22, 1.84) HDL-c <0.001 0.24 (0.11, 0.50) LDL-c 0.249 1.14 (0.91, 1.43) APOE*ε4 carriers 0.079 1.73 (0.94, 3.18) CETP*V carriers 0.015 1.88 (1.13, 3.12) Adjusted For APOE*ε4a 0.010 1.96 (1.17, 3.27) Adjusted For age BMI drinkb 0.047 1.74 (1.01, 2.99) Adjusted For TC,HDL-c,LDL-cc 0.036 2.15 (1.05, 4.40) CETP*V - APOE*ε4 carriersd 0.001 4.36 (1.85, 8.28) CETP*V× APOE*ε4 interactione 0.002 3.25 (1.52, 6.93) 0 1 4 10

Fig. 1. Univariate/multivariable-adjusted logistic regression for the risk factors of hTG in oldest-old females. a Risk for hTG of CETP*(VV + VI:II) adjusted for APOE*4. b Risk for hTG of CETP*(VV + VI:II) adjusted for age, BMI, alcohol drinking. c Risk for hTG of CETP*(VV + VI:II) adjusted for TC, TG, HDL-c, and LDL-c. d Risk for CETP*V-APOE*4 carriers [CETP*(VV + VI)-APOE*(ε2ε4 + ε3ε4 + ε4ε4)]. e Interaction item estimated by logistic regression.

with this observation, TG level was significantly higher in subjects with CETP*V than those with CETP*I.

Conflict of interest