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 Dr. Mitsuru Murata, Keio University School of MedicineIt is extremely frequent in the Omagari area of Japan: marked hyperalphalipoproteinemia caused by CETP gene mutation is not associated with longevity. Arteriosclerosis, Thrombosis, and Vascular Biology. Reference is associated with longevity in centenarians in Japan, where the prevalence of the deficiency is extremely high. In addition, despite a significant impact of several genetic polymorphisms in RCT on plasma HDL-C concentrations in centenarians, there was no frequency difference between centenarians and controls for these polymorphisms. These results, however, should be interpreted cautiously. There could be several reasons for our negative results. First, it may be true that those loci have no impact on longevity. Our results were in line with those of Bladbjerg et al. [22] that demonstrated no associations of 11 gene polymorphisms chosen for their potential risk for CAD with longevity for Danish centenarians. These findings suggest the possibility that the genetic polymorphisms which have antiatherogenic or proatherogenic property could have no significant impact on longevity. Second, centenarians have been exposed during their lifetime to a very different environment than the control population and in other populations around the world where these loci have been examined for lipid metabolism and CAD risk. In the 1970s when centenarians were most susceptible to CAD, their daily intake of fat was less than 10% of the calories in the Japanese population; however, nowadays it rises to 25% and over (Ministry of Health and Welfare, National Nutrition Survey in Japan, 2000). Considering the low risk for CAD in the population and the low-fat diet traditionally consumed in Japan, it is not surprising that candidate genes for lipid metabolism have little effect on longevity. Third, it is possible that our study design and sample size may not have enough statistical power to address this issue. Further DNA polymorphisms at the lipoprotein lipase gene: associations in normal and hypertriglyceridemic subjects. Atherosclerosis. Wang XL, Mredie RM, Wilcken DE (1996) Common DNA polymorphisms at the lipoprotein lipase gene: association with severity of coronary artery disease and diabetes. Circulation. Gerdes C, Gerdes LU, Hansen PS, Faergeman O (1997) Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 60-year-old Danish men. Circulation. Holmer SR, Hengstenberg C, Mayer B, Dring A, Lwel H, Engel S, Hense HW, Wolf M, Klein G, Riegeger AJ, Schunkert H (1998) Lipoprotein lipase gene polymorphism, cholesterol subfractions and myocardial infarction in large samples of the general population. Cardiovascular Research. Vohl MC, Lamarche B, Moorjani S, Prudhomme D, Nadeau A, Bouchard C, Lupien PJ, Despres JP (1998) The lipoprotein lipase Hindpolymorphism modulates plasma triglyceride levels in visceral obesity. Arteriosclerosis Thrombosis and Vascular Biology. Clee SM, Zwinderman AH, Engert JC, Zwarts KY, Molhuizen HO, Roomp K, Jukema JW, van Wijland M, van Dam M, Hudson TJ et al. (2001) Common genetic variation in ABCA1 is associated with altered lipoprotein levels and a modified risk for coronary artery disease. Circulation. Lutucuta S, Ballantyne CM, Elghannam H, Gotto AM Jr., Marian AJ (2001) Novel polymorphisms in promoter region of ATP binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy. Circulation Research. Tato F, Vega GL, Grundy SM (1983) Determinants of plasma HDL-cholesterol in hypertriglyceridemic patients: role of cholesterol-ester transfer protein and lecithin cholesteryl acyl transferase. Arteriosclerosis Thrombosis and Vascular Biology. Nishiwaki M, Ishikawa T, Ito T, Shige H, Tomiyama K, Nakajima K, Kondo K, Hashimoto H, Saitoh K, Manabe M, Miyajima E, Nakamura H (1997) Effects of alcohol on lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein and lecithin:cholesterol acyltransferase in high-density lipoprotein cholesterol elevation. Atherosclerosis. Schter F, Fauer-Delanef L, Guenot F, Rouge H, Froguel P, Lesueur-Gin