Taking into account that several mechanisms have beenThe apoptosis pathway may account for the association with inflammation and AMI. However, it should be noted that there are currently no reports showing the association between MEFV mutations and CHD, only studies regarding the absence of disease in FMF patients treated with colchicine [26] (see also Introduction). Inflammatory pathways have been studied extensively [1-4]. The MEFV gene is expressed in early leukocyte development and is regulated in response to inflammatory mediators [5]. The familial Mediterranean fever protein, pyrin, associates with microtubules and colocalizes with actin filaments [6]. Familial Mediterranean fever is not a rare disease in Italy [7] and the spectrum of FMF mutations has been studied [8]. Furthermore, studies have been conducted on the mutation and haplotype of familial Mediterranean fever which have revealed new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population [9-11]. Common mutations in the familial Mediterranean fever gene associate with rapid progression to disability in non-Ashkenazi Jewish multiple sclerosis patients [12]. Acute phase response and evolution of familial Mediterranean fever have also been studied [13-15]. The three most common MEFV mutations have been analyzed in patients with familial Mediterranean fever [16] and genotype-phenotype assessment of common genotypes among patients with familial Mediterranean fever has also been conducted [17]. Moreover, genetic susceptibility to death from coronary heart disease has been studied in a twin study [18]. A gender-dependent genetic predisposition to produce high levels of IL-1β is detrimental for longevity [19]. Allele frequencies of T>A single nucleotide polymorphism at the first intron of interferon-γ gene in a group of Italian centenarians have also been studied [20]. An association between IL-1β promoter polymorphism and longevity has been reported [21], as well as further studies on the protective effects in men of IL-1β promoter SNP and its interaction with TNF-α promoter SNP [22]. Prevalence of ischemic heart disease in patients with familial Mediterranean fever has been studied [23] and genotype-phenotype correlation in a large group of Turkish patients with familial Mediterranean fever has been demonstrated [24]. In conclusion, the present results add another piece of evidence to our hypothesis that people genetically predisposed to a weak inflammatory activity have less chance to develop CHD and therefore, a greater chance to live longer in a modern environment with reduced pathogen load and improved control of severe infections by antibiotics [14, 22-25, 31, 36]. In any case, all these data point out the strong relationship among inflammation, genetics, CHD, and longevity. Finally, our comparison with centenarians may help to elucidate the role of genetics in age-associated inflammatory diseases characterized by a multifactorial etiology. This work was supported by grants from the Italian Ministry of Education, University and Research to G. Candore, D. L., G. C-R., and C. C. Funds from Italian Ministry of Health (genetic and nongenetic factors of health in elderly) to C. F. and G. C-R. are also acknowledged. M. P. G. and S. V. are Ph.D. students of the Pathobiology Ph.D. course (directed by C. C.) of Palermo University, and this work is in partial fulfillment of the requirement for the Ph.D. Statistical advice from Prof. C. Camma` is acknowledged.

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