Role of the pyrin M694V (A2080G) allele in acute myocardial infarction and longevity: a study in the Sicilian population.
A proinflammatory genotype seems to contribute significantly to the risk of developing coronary heart disease (CHD). Conversely, the susceptibility alleles to inflammatory disease should be infrequent in the genetic background favoring longevity. In fact, in a modern environment, attainment of longevity is facilitated by an anti-inflammatory status. 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.
Grimaldi
Maria Paola
MP
Dipartimento di Biopatologia e Metodologie Biomediche, Universitá di Palermo, Italy.
Candore
Giuseppina
G
Vasto
Sonya
S
Caruso
Marco
M
Caimi
Gregorio
G
Hoffmann
Enrico
E
Colonna-Romano
Giuseppina
G
Lio
Domenico
D
Shinar
Yael
Y
Franceschi
Claudio
C
Caruso
Calogero
C
D000208:Acute Disease / Q000453:epidemiology; D000328:Adult; D000367:Age Factors; D000369:Aged, 80 and over; D000483:Alleles; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D004777:Environment; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009203:Myocardial Infarction / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D000071198:Pyrin; D012307:Risk Factors; D012802:Sicily / Q000453:epidemiology
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D020033:Protein Isoforms; D000071198:Pyrin