effects of mutations and the Taq1B the CETP gene, and the LPL PvuII genotype on levels among centenarians and controls are Tables 3 and 4, respectively. Both in centenarians heterozygous CETP deficiencies including 14 and exon 15 were consistently associated HDL-C concentrations (P=0.0003 and t test, respectively) and with markedly CETP concentration (P<0.0001 and t test, respectively). In regard to the genotype, the B2 allele was significantly with lower CETP mass and higher HDL-C in control (P=0.0387 and P=0.029, ANOVA, and a similar but nonsignificant trend was in centenarians. The B2 allele was lower low-density lipoprotein cholesterol in (P=0.024). There was a significant − P( ) allele of the LPL gene with lower higher HDL-C concentrations in centenarians, relationship was not observed in controls. There significant association between ABCA1 genotype parameters either in centenarians or in the LPL HindIII polymorphism nor the promoter polymorphism had significant with lipid parameters in centenarians and are not shown). When men and women were separately, the same results as shown in Table observed in centenarians of both sexes, statistical power was less in male centenarians. however, there was a significant association

Fig. 1 Alleles frequencies of genes involved in reverse cholesterol transport between centenarians and controls. Comparison of al- leles frequencies between centenarians and controls were calculat- ed by χ2 test. No significant difference was observed

Two common CETP deficiencies, an intron 14 splic- ing defect [4] and an exon 15 missense mutation [5], have been reported in the Japanese population. In this study there was no subject who was identified as homo- zygous CETP deficiency. There was no difference in fre- quencies of either type of heterozygous CETP deficien- cies between centenarians and controls. The distributions of the Taq1B polymorphism of the CETP gene, the LPL PvuIIand HindIII genotype, the C-514T polymorphism of the HL gene and recently identified R219K variant of the ABCA1 gene did not differ between centenarians and controls.

for CETP mutations using unpaired t test (TC total cholesterol, LDL-C low-density lipoprotein cholesterol, HDL-C high-density lipoprotein cholesterol, TG triglyceride, CETP cholesteryl ester transfer protein)

Table 3 Body mass index (BMI), albumin, and lipid fractions in centenarians in relation to deficiency and Taq1B genotype of CETP and LPL PvuII genotype; statistical significance for LPL PvuII and ABCA1 R219K genotype were calculated using ANOVA,

Genotype n Sex: BMI Albumin TC LDL-C HDL-C TGa CETP M/F (g/dl) (mg/dl) (mg/dl) (mg/dl) (mg/dl) (µg/ml) CETP deficiency Deficiency 18 12/6 20.3±3.3 3.7±0.4 171±32 89±28 61±22** 109±44 1.8±0.4** Wild type 238 178/60 19.1±3.6 3.6±0.4 162±32 93±26 51±13** 91±39 3.3±0.8** CETP Taq1B B1B1 73 51/22 19.4±4.7 3.6±0.4 169±36 100±30* 51±13 94±41 3.3±1.1 B1B2 132 101/31 19.0±3.0 3.5±0.4 159±29 90±24* 51±13 93±39 3.1±0.9 B2B2 51 38/13 19.4±3.2 3.6±0.5 162±34 89±26* 55±17 92±40 3.0±0.8 LPL PvuII P(−/−) 20 18/2 18.7±3.1 3.6±0.5 163±38 88±30 61±18* 71±23* 3.3±1.2 P(−/+) 101 77/24 19.0±3.6 3.5±0.4 163±32 95±28 50±12* 92±42* 3.0±0.9 P(+/+) 135 95/40 19.4±3.7 3.6±0.4 162±31 92±25 51±15* 97±39* 3.2±0.9

* P<0.05 by ANOVA, **P<0.05 by unpaired t test a Logarithmically transformed values were used for statistical analysis but pretransformed values are expressed

CETP mutations was calculated unpairedt test (TC total cholester- ol,LDL-C low-density lipoprotein cholesterol, HDL-C high-densi- ty lipoprotein cholesterol, TG triglyceride, CETP cholesteryl ester transfer protein)

Table 4 Body mass index (BMI), albumin, and lipid fractions in controls in relation to deficiency and Taq1B genotype of CETP and LPL PvuII genotype; statistical significance for LPL PvuII and ABCA1 R219K genotype were calculated using ANOVA, for

Genotype n. Sex: BMI Albumin TC LDL-C HDL-C TGa CETP M/F (g/dl) (mg/dl) (mg/dl) (mg/dl) (mg/dl) (µg/ml) CETP deficiency Deficiency 16 9/7 22.3±3.4 4.7±0.1 184±33 101±34 72±19** 71±32 2.7±0.6** Wild type 174 95/79 22.8±3.1 4.6±0.1 192±35 110±32 60±14** 121±88 3.8±0.9** CETP Taq1B B1B1 65 37/28 21.6±3.0 4.6±0.4 179±32 99±30 58±15* 103±69 4.0±1.2** B1B2 84 45/39 22.3±3.4 4.7±0.3 188±40 106±33 58±12* 117±96 3.6±0.8** B2B2 41 22/19 21.6±2.9 4.6±0.3 181±34 98±31 65±16* 91±60 3.4±0.5** LPL PvuII P(−/−) 14 6/8 22.3±3.6 4.8±0.2 185±45 109±40 56±10 100±74 3.1±14 P(−/+) 71 41/30 22.1±3.4 4.7±0.3 177±33 96±30 60±15 104±96 3.8±0.8 P(+/+) 105 57/48 22.1±3.1 4.7±0.4 188±37 105±31 60±14 111±72 3.7±1.0

*P<0.05 by ANOVA, **P<0.05 by unpaired t test a Logarithmically transformed values were used for statistical analysis but pretransformed values are expressed

Table 6 Multiple regression analysis of high-density lipoprotein cholesterol as dependent and age, body mass index (BMI), sex, cholesteryl ester transfer protein (CETP) deficiency, CETP Taq1B, and lipoprotein lipase (LPL)PvuII(−/−) genotype as independent variables in controls

Table 5 Multiple regression analysis of high-density lipoprotein cholesterol as dependent and body mass index (BMI), sex, serum albumin, cholesteryl ester transfer protein (CETP) deficiency, CETP Taq1B, and lipoprotein lipase (LPL)PvuII(−/−) genotype as independent variables in centenarians

Cumulative r2 F P Sex 0.230 50.1 <0.0001 BMI 0.277 31.0 <0.0001 CETP deficiency 0.320 25.3 <0.0001 CETP Taq1B genotype 0.337 21.8 <0.0001

Cumulative r2 F P Albumin 0.226 72.4 <0.0001 CETP deficiency 0.246 9.9 <0.0001 LPL PvuII genotype 0.267 2.9 <0.0001

tween the HL C allele and lower total cholesterol con- centration only in men (P=0031, ANOVA).

in HDL-C concentrations in centenarians and (Tables 5 and 6, respectively). As previously de- by us [23], serum albumin was the most power- predictor of HDL-C in centenarians (r2=0.226, P<0.0001). CETP deficiency and the LPL PvuII were also independently associated with HDL-