The text seems to be an academic article discussing the role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity. Here's the processed text:

Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population.

Maria Paola Grimaldi,* Giuseppina Candore,* Sonya Vasto,* Marco Caruso, Gregorio Enrico Hoffmann, Giuseppina Colonna-Romano,* Domenico Lio,* Yael Shinar, Claudio Franceschi, and Calogero Caruso*,1 *Gruppo di Studio sullImmunosenescenza, Dipartimento di Biopatologia e Metodologie Biomediche, and Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche, Universita` di Palermo, Italy; Heller Institute of Medical Research, Sheba Medical Center, Tel Hashomer, Israel; and Dipartimento di Sperimentale and Centro Interdipartimentale L. Galvani, Universita` di Bologna, and Istituto Nazionale di  gevity [14]. The Mediterranean fever gene MEFV is highly polymorphic among the Mediterranean populations and is proposed to play an important role in controlling the leukocyte-related inflammatory responses and apoptosis [58]. The MEFV gene encodes for pyrin, a basic protein of 781 amino acids, expressed in the cytosol of neutrophils, eosinophils, and activated monocytes. Although its exact mode of function is not known, its N-terminal, similar in secondary structure to the death protein domains, is capable of binding to key molecules in inflammatory gene transcription and cytokine secretion [8]. Proinflammatory activators up-regulate leukocyte MEFV message levels, whereas anti-inflammatory cytokines down-regulate them [9-11]. So far, the role of MEFV in cardiovascular diseases has not been formally demonstrated (see below), and its effect on longevity has not yet been studied. 

To evaluate whether inflammatory alleles of pyrin, the gene responsible for familial Mediterranean fever (FMF), may play an opposite role in CHD and in longevity, we examined three FMF-associated mutations, M694V (A2080G), M694I (G2082A), and V726A (T2177C), encoded by the FMF gene (MEFV) in 121 patients affected by acute myocardial infarction (AMI), in 68 centenarians, and in 196 age-matched controls from Sicily. None of the Sicilian subjects studied carried the V726A and the M694I FMF-related mutations. The proinflammatory M694V (A2080G) mutation was the only one we found which was over-represented significantly in CHD patients and under-represented in oldest old, and intermediate values were in healthy young controls. After adjustment for well-recognized AMI risk factors, the M694V allele still predicted a significant risk to develop AMI. So, according to these results, we suggest that carrying the proinflammatory M694V pyrin allele may increase the risk to develop AMI. Conversely, the wild-type pyrin genotype may predispose to a greater chance to live longer in a modern environment with reduced pathogen load and improved control of severe infections by antibiotics. All these data indicate a strong relationship among inflammation, genetics, CHD, and longevity. J. Leukoc. Biol. 79: 611-615; 2006.

The most prevalent mutations in the MEFV gene are ancient founder mutations, which are associated with familial Mediterranean fever (FMF) [6, 8]. The disease is an autosomal, recessive, inflammatory disorder, characterized by fever attacks combined with abdominal, chest, or joint pain, erysipelas-like erythema, and infiltration of affected tissues by large numbers of neutrophils [9]. FMF is an ethnically restricted genetic disease, found commonly among Mediterranean populations such as Jews, Turks, Arabs, and Armenians. However, in the course of time, as a result of several migrations, the Mediterranean MEFV alleles reached Western Europe, spreading throughout Italy, France, and Spain. Further, FMF is also found in Ashkenazi Jews (Eastern European origin), although less frequently [12, 13].

Langevitz et al. [26] also reported on a higher prevalence of CHD in families of FMF patients than in controls (their spouses). Yet this observation was not attributed to the high probability of mutation carriers among these family members, and therefore their genotype was not pursued.

Blood specimens were collected in tripotassium EDTA sterile tubes, DNA-extractedProtocols [27] were followed, and random samples were genotyped using restriction enzyme site analysis at the Heller Institute, Sheba Medical Center (Tel Hashomer, Israel), to confirm the results [20]. Allele and genotypic frequencies were evaluated by gene count, and differences in frequency among the groups were assessed. The chi-square test (2x2 and 3x2 tables, where appropriate) and odds ratio (OR) with a confidence interval (CI) were calculated. The data were tested for goodness of fit between the observed and expected genotype frequencies according to the Hardy-Weinberg equilibrium (HWE) by chi-square test. In male patients and controls, we performed a logistic regression analysis to test the association of genotypes with AMI after adjusting for smoking habits, family history of CHD, and the presence of Type 2 diabetes, obesity, hypertension, hypercholesterolemia, and hypertriglyceridemia. The OR (with CI) was calculated as the exponential of the regression coefficient and its standard error. We studied three MEFV mutations commonly seen in the Mediterranean area, M694V, M694I, and V726A [19, 20], in patients affected by AMI and age-matched controls from Sicily. First, to improve the power of our study, we selected genetically loaded cases having early AMI onset (<46 years) [21]. Second, we studied a third group of subjects consisting of a cohort of Sicilian centenarians. In our previous studies, we demonstrated that achievement of longevity is facilitated by an anti-inflammatory status [22-25], and centenarians are a suitable control group for complex, age-related inflammatory diseases such as coronary heart disease (CHD) [14].

RESULTS