Young controls Centenarians   AMI patients (M694V genotypes) P 0.009 OR 2.2 (1.3–4.1) P 0.003 OR 4.2 (1.5–11.3)   AMI patients (M694V alleles) P 0.009 OR 2.1 (1.2–3.6) P 0.004 OR 3.7 (1.4–9.8)

The frequency of proinflammatory genotypes and alleles in centenarians was lower (but not significantly) than that observed in the young control cohort. After adjustment for smoking habits, family history of CHD, and the presence of Type 2 diabetes, obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia, significant differences in genotype frequency persisted between male AMI patients and male centenarians [P(cid:6)0.033; OR 1.10 (1.01–1.18)] and between male AMI patients and male young controls [P(cid:6)0.0007; OR 1.10 (1.04–1.16)].

elevated WBC counts show a higher risk of developing AMI [29]. A possible link, which is working to increase procoagu- lant activity of circulating leukocytes, has been proposed be- tween the inflammation and thrombosis in CHD patients [29]. Thus, the presence of mutations in the gene of pyrin, causing the survival of leukocytes, which would otherwise be direct to the apoptosis pathway, might account for the association with inflammation and AMI. However, it must be pointed out that until now, there are no reports showing the association between MEFV mutations and CHD but only studies regarding the absence of disease in FMF patients treated with colchicine [26] (see also Introduction).

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T

A

In conclusion, the present results add another piece of evidence to our hypothesis that people genetically predisposed to a weak inflammatory activity have less of a chance to develop CHD and therefore, a greater chance to live longer in a modern environment with reduced pathogen load and im- proved control of severe infections by antibiotics [1–4, 22–25, 31, 36]. In any case, all these data point out the strong relationship among inflammation, genetics, CHD, and longev- ity. Finally, our comparison with centenarians may help to elucidate the role of genetics in age-associated inflammatory diseases characterized by a multifactorial etiology.

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American referrals to the National Institutes of Health. Medicine (Baltimore)

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Aksentijevich, I., Torosyan, Y., Samuels, J., Centola, M., Pras, E., J. J., Oddoux, C., Wood, G., Azzaro, M. P., Palumbo, G., Giustolisi, Pras, M., Ostrer, H., Kastner, D. L. (