CETP deficiency raises HDL cholesterol in Japanese centenarians but does not affect longevity (J Mol Med (Berl) 2003)

Cholesteryl ester transfer protein (CETP) is one of the key proteins in reverse cholesterol transport (RCT). The role of CETP in atherosclerosis remains controversial. In this study we investigated the associations between polymorphisms of CETP (mutations in intron 14 and exon 15, and Taq1B), hepatic lipase (C-514T), lipoprotein lipase ( PvuII and HindIII), and ATP-binding cassette transporter 1 (R219K) loci and longevity in 256 centenarians and 190 healthy younger controls. Although heterozygous CETP deficiency and the B2 allele of the Taq1B polymorphism was consistently associated with higher HDL-C concentrations both in centenarians and controls, the allelic frequencies of those polymorphisms did not differ between the two groups. The allelic frequencies of other gene polymorphisms in RCT were not different between the two groups. Centenarians with lipoprotein lipase P(-/-) genotype had significantly higher HDL-C concentration than those with P(-/+) or with P(+/+), in contrast, there was no such a relationship among controls. In stepwise multiple regression analysis, serum albumin, CETP deficiency and lipoprotein lipase PvuII genotype were independently associated with HDL-C in centenarians. Sex, CETP deficiency, and the Taq1B genotype were also independently associated with HDL-C; however, lipoprotein lipase PvuII genotype had no significant effect on their HDL-C in controls. In conclusion, we observed that CETP deficiency and other gene polymorphisms in RCT have no impact on longevity for Japanese centenarians.