Genotype Predicts Phenotype: Longevity, Lipoproteins, and Cognition

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Genotype Predicts Phenotype: Longevity, Lipoproteins, and Cognition

In very long-lived Ashkenazi Jews, the CETP VV genotype is associated with protection against cognitive decline.

In centenarians, the relative frequency of the VV genotype variant of cholesterol ester transfer protein (CETP) is increased threefold in comparison with younger individuals, and the variant is associated with reduced cardiovascular risks. These researchers hypothesized that the protective effects of this genotype extend to cognitive function.

In 158 Ashkenazi Jews (age range, 95–107), cognitive function was evaluated with the Mini-Mental State Examination (MMSE). Individuals with MMSE scores greater than 25 were twice as likely to have the CETP VV genotype as those with scores of 25 or less (29% vs. 14%), a significant difference. They also had higher plasma levels of high-density lipoprotein (HDL) and larger-size HDL particles. The authors conclude that the CETP VV genotype is protective against age-associated cognitive decline and is associated with clinically relevant effects on lipoprotein patterns.

Comment: This study provides new evidence that, for cognitive function and longevity, genotype may determine phenotype. Consistent with many recent clinical studies, the findings also offer supportive evidence that cardiovascular factors have an important role in cognitive health. Whether these results are relevant for the non-Ashkenazi population remains unknown, but understanding the precise mechanisms by which the CETP gene and associated lipoprotein characteristics influence cognition may improve efforts to maintain the integrity of the aging brain and might lead to drugs that mimic the protective effects of this genotype.

— John C. Morris, MD

Dr. Morris is Harvey A. and Dorismae Friedman Distinguished Professor of Neurology, Washington University School of Medicine, St. Louis, MO.

Published in Journal Watch Neurology January 23, 2007