Genetics
A CETP gene variant favors healthy survival past age 90 in long-lived Japanese-American men (J Gerontol A Biol Sci Med Sci 2008)
Original title: A prospective study of high-density lipoprotein cholesterol, cholesteryl ester transfer protein gene variants, and healthy aging in very old Japanese-american men
Since CETP deficiency mutations that raise HDL cholesterol have been linked to exceptional longevity, yet a clinical trial of a potent CETP inhibitor was terminated for increased mortality, researchers examined HDL cholesterol, CETP genetic variants (CD442G and Int 14A) and longevity phenotypes in 3562 Japanese-American men from the Honolulu Heart Program, followed for up to 8 years from average age 78 to average age 84. Low HDL cholesterol was a risk factor for cardiovascular mortality (P equals .002) but not for non-cardiovascular or total mortality after adjustment. Men carrying the CETP Int 14A variant had higher HDL cholesterol (P equals .047), a trend toward lower mortality, and were significantly more likely to be healthy survivors beyond age 90, free of six major age-related diseases with high physical and cognitive function (P equals .005), suggesting high HDL cholesterol and the Int 14A CETP variant may favor healthy aging.
Original abstract
Background: High-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP) gene deficiency mutations that increase HDL-C levels have been associated with exceptional longevity. However, a recent clinical trial of a promising CETP inhibitor that markedly increases HDL-C was terminated due to increased mortality. In light of this controversy, we examined the relationship among HDL-C, CETP mutations, and longevity phenotypes in the long-lived Japanese-American men of the Honolulu Heart Program (HHP).
Methods: Japanese-American men (n = 3562) were followed for up to 8 years, from average age 78 to average age 84 (maximum age 99), or until death. Total mortality, cause-specific mortality, and healthy survival were evaluated for associations with HDL-C level and CETP genetic variants common in the Japanese population (CD442G and Int 14A).
Results: HDL-C was negatively associated with cardiovascular disease (CVD) mortality (p =.002) but not related to non-CVD (p =.147) or total (p =.547) mortality after adjustment for common risk factors. There was a trend for lower mortality for the men with the Int 14A variant. These men also had higher HDL-C levels (p =.047) and were significantly more likely to be healthy survivors (absence of six major age-related diseases and high physical/cognitive function) beyond the age of 90 years (p =.005).
Conclusions: Low HDL-C level is a risk factor for CVD mortality in elderly Japanese-American men. High HDL-C and the Int 14A variant of the CETP gene may increase odds for healthy aging.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.