title: Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity.
abstract: Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The alpha1-antitrypsin (AAT) is a serine-protease inhibitor required for the prevention of proteolytic tissue damage, by neutrophil elastase. The role of AAT in CVD has not been definitively assessed and its effect on longevity has not yet fully been studied. To clarify these points, we have studied the distribution of AAT allele variants in 3 cohorts: 127 young patients affected by acute myocardial infarction (AMI), 255 young controls and 143 centenarians from Sicily. The Z allele frequency was most frequent in centenarians (13.3%), intermediate in healthy young controls (3.1%) and less frequent in AMI patients (1.2%) (P = 0.0000001). The heterozygous MZ genotype was significantly over represented in centenarians (38/143) and under represented in AMI patients (3/127) with intermediate values in young controls (16/255) (P = 0.0000001). After adjustment for well-recognized AMI risk factors, the MZ genotype still predicted a significant negative risk factor for developing AMI in the Sicilian population. Thus, our data show a positive role of MZ heterozygosity in attainment of successful ageing linked to the positive effects of this genotype versus the cardiovascular ischemic diseases.
authors.affiliation: Dipartimento di Biopatologia e Metodologie Biomediche, Gruppo di Studio sull'Immunosenescenza, Corso Tukory 211, Palermo 90134, Italy.
authors.forename: Florinda
authors.initials: F
authors.lastname: Listì
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Candore
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Grimaldi
authors.forename: Domenico
authors.initials: D
authors.lastname: Lio
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Colonna-Romano
authors.forename: Valentina
authors.initials: V
authors.lastname: Orlando
authors.forename: Marco
authors.initials: M
authors.lastname: Caruso
authors.forename: Enrico
authors.initials: E
authors.lastname: Hoffmann
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Calogero
authors.initials: C
authors.lastname: Caruso
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D012802:Sicily; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: C043392:SERPINA1 protein, human; D000515:alpha 1-Antitrypsin