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February 25, 2004

Genetic Factors in Exceptional Longevity

Author Affiliations

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2004;291(8):941-943. doi:10.1001/jama.291.8.941-b

To the Editor: Dr Barzilai and colleagues1 reported that families with exceptional longevity have significantly larger high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particle sizes, which are associated with increased homozygosity for the codon 405 isoleucine to valine (I405V) variant in the cholesteryl ester transfer protein (CETP) gene. These results, however, are at odds with previous studies. For instance, this genotype has been associated with increased risk of coronary artery disease (CAD) in the Copenhagen City Heart study.2 Studies have also found that genetically determined deficiency of CETP activity may contribute to increased levels of possibly dysfunctional HDL cholesterol, which may actually increase risk of ischemic heart disease.2 Based on 1749 consecutive patients with acute myocardial infarction, we have reported that this genotype is correlated with the extent of CAD on angiography.3 Finally, homozygosity for this allele was not found to be independently associated with CAD in a study that evaluated 112 candidate gene variants in 5061 individuals of Japanese origin.4

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