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Deficiency of choresteryl ester transfer protein and gene polymorphisms of lipoprotein lipase and hepatic lipase are not associated with longevity

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Abstract

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.

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Abbreviations

ABCA1 :

ATP-binding cassette transporter 1

ANOVA :

Analysis of variance

apo :

Apolipoprotein

CAD :

Coronary artery disease

CETP :

Cholesteryl ester transfer protein

HDL-C :

High-density lipoprotein cholesterol

HL :

Hepatic lipase

LPL :

Lipoprotein lipase

PCR :

Polymerase chain reaction

RCT :

Reverse cholesterol transport

RFLP :

Restriction fragment length polymorphism

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Acknowledgements

We sincerely thank the centenarians and their family members for their time and assistance. We could not have carried out this study without their kind cooperation. This study was partially supported by a grant from the Ministry of Health and Welfare for the Scientific Research Project for Longevity and a grant for studying the sociomedical background of centenarians (Principal investigator, Nobuyoshi Hirose) as well as aid for research from Keio Health Consulting Center. We wish to thank to Dr. Mitsuru Murata, Keio University School of Medicine, for his assistance in statistical analysis.

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Correspondence to Yasymichi Arai.

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Arai, Y., Hirose, N., Yamamura, K. et al. Deficiency of choresteryl ester transfer protein and gene polymorphisms of lipoprotein lipase and hepatic lipase are not associated with longevity. J Mol Med 81, 102–109 (2003). https://doi.org/10.1007/s00109-002-0407-6

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