Apolipoprotein C3 gene associated with longevity

April 03, 2006

New York, NY - A team from Albert Einstein College of Medicine has identified a second longevity gene occurring more frequently in people who live to 100 years of age [1]. These centenarians display a polymorphism in the apolipoprotein C3 (APOC3) gene that results in them having better cardiovascular risk profiles than control subjects.

The research is reported online April 3, 2006 in PLoS Biology by Dr Gil Atzmon and colleagues: the same group published work in the Journal of the American Medical Association three years ago detailing the first gene found in centenarians associated with longevity.

In that paper, 25% of the 100-year-olds had a specific mutation of the cholesteryl-ester-transfer-protein (CETP) gene, which meant that they had significantly larger high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles.

Centenarians had lower LDLs, triglycerides, and cholesterol; higher HDL

Now, using the same group of 214 Ashkenazi Jews who have passed or nearly reached 100, Atzmon and his team have found a polymorphism in the APOC3 gene. They also examined 216 offspring of these centenarians and an age-matched Ashkenazi group as controls (n=258).

The polymorphism replaces an A (adenine) nucleotide with a C (cytosine) in the gene. The frequency of the CC polymorphism occurring in both copies of the gene was 25% among centenarians, 20% in their offspring, and 10% in the control subjects (p=0.0001 and p=0.001, respectively).

All those carrying the CC polymorphism "had lower LDLs, lower triglycerides, lower total cholesterol, and higher HDL levels" than those who didn't have the mutation, Atzmon told heart wire . In addition, the CC carriers had a lower prevalence of hypertension and greater insulin sensitivity, suggesting a protective effect against cardiovascular disease and the metabolic syndrome, he says.

However, he added that there are, as yet, "few clinical implications of these new findings." But he pointed to his group's previous work and the development of CETP inhibitors, such as Pfizer's torcetrapib, which are nearing the market and are designed to increase HDL levels, as evidence of the potential of these basic findings.

The team has identified another gene associated with longevity, details of which are due to be published shortly, Atzmon added.

These favorable lipoprotein profiles in the very elderly reported by the New York team also correlate with other studies of Japanese and Italian centenarians.

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