In contrast, no significant difference was observed between centenarians and controls for the ACE I/D polymorphism. 

Overall, this study provides additional evidence supporting an association between APOE polymorphisms and longevity in French centenarians. However, it is important to note that while statistically significant, the borderline level of significance observed for some associations precludes definite conclusions.cardiovascular disease: evidence from the ECTIM study. Strasbourg and Toulouse were used in the study, as well as non-related individuals from the CEPH families without documented birthplaces. It is important to match cases and controls for geographic origin because allele frequencies can vary regionally. Additionally, the laboratory that genotyped the ECTIM individuals for the control group in 1994 was different from the one that typed the centenarians. It is preferable to genotype all cases and controls in the same place and at the same time to minimize genotyping errors which can vary between different laboratories. The excess of the D allele for French centenarians reported in 1994 was not confirmed in this study. Several authors have examined the ACE association with longevity since then, but results have been inconsistent. Cases and controls were matched for sex and geographic origin, with each control defined as an individual whose parents were both born in the same region as that of the centenarian. This procedure samples the population at a time when population mobility was low and minimizes the effect of population immigration. The initial report of the association of ACE with longevity in French centenarians was based on a 6% difference in the D allele frequency, which may be affected by regional variation within France. Accurate genotyping of the I/D polymorphism of ACE requires reliable amplification of two DNA fragments markedly different in molecular size for D and I alleles. Sub-optimal PCR conditions can lead to misclassification of I/D heterozygotes as D/D homozygotes, resulting in overestimation of D allele frequency. Repeat genotyping by us revealed discrepancies in 17 of 338 individuals reported in 1994, suggesting that genotyping errors may have led to overestimation of D allele frequency in the centenarian population. Matching cases and controls is essential, and robust and standardized genotyping protocols should be used on large numbers of samples. The association of the APOE polymorphism with longevity was confirmed in this study, but the association of the ACE D allele with longevity in the French population was not replicated. It is likely that such an association exists in this population, but it would require much larger groups to be reliably demonstrated.Myocardial infarction. The ECTIM Study, Arteriosclerosis. Thromb. 14. [26] Faure-Delanef L., Baudin B., Benteau-Burnat B., Beaudoin J.C., Giboudeau J., Cohen D., Plasma concentration, kinetic constants, and gene polymorphism of angiotensin I-converting enzyme in centenarians, Clin. Chem. 44 (1998) 2083-2087. [22] Lonjou C., Clayton J., Cambon-Thomsen A., Raffoux C., HLA-A, -B, -DR haplotype frequencies in France - implications for recruitment of potential bone marrow donors, Transplantation 60 (1995) 375-383. [27] Lindpaintner K., Pfeffer M.A., Kreutz R., Stampfer M.J., Grodstein F., LaMotte F., Buring J., Hennekens C.H., A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease, N. Engl. J. Med. 332 (1995) 706-711. [23] Lucotte G., Loirat F., Hazout S., Pattern of gradient of apolipoprotein E allele *4 frequencies in western Europe, Hum. Biol. 69 (1997) 253-262. 135