TY - JOUR
T1 - Alpha-1 antitrypsin heterozygosity plays a positive role in attainment of longevity
AU - Colonna Romano, Giuseppina
AU - Caruso, Calogero
AU - Hoffmann, Enrico
AU - Lio, Domenico
AU - Candore, Giuseppina
AU - Orlando, Valentina
AU - Franceschi, Claudio
AU - Colonna-Romano, Giuseppina
AU - Listì, Florinda
AU - Lio, Domenico
AU - Candore, Giuseppina
AU - Grimaldi, Maria Paola
AU - Paolisso, Giuseppe
AU - Caruso, Calogero
AU - Listi', Florinda
AU - Grimaldi, Maria Paola
AU - Orlando, Valentina
PY - 2007
Y1 - 2007
N2 - Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The a1-antitrypsin (AAT) is a serineprotease 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 ischemicdiseases.
AB - Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The a1-antitrypsin (AAT) is a serineprotease 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 ischemicdiseases.
UR - http://hdl.handle.net/10447/5790
M3 - Article
VL - 8
SP - 139
EP - 145
JO - Biogerontology
JF - Biogerontology
SN - 1389-5729
ER -