Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity

Florinda Listì, Giuseppina Candore, Maria Paola Grimaldi, Domenico Lio, Giuseppina Colonna-Romano, Valentina Orlando, Marco Caruso, Enrico Hoffmann, Giuseppe Paolisso, Claudio Franceschi, Calogero Caruso

Research output: Contribution to journalArticle

Abstract

Genes involved in cardiovascular diseases (CVD) play an opposite role in human longevity. The α1-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.

Original languageEnglish
Pages (from-to)139-145
Number of pages7
JournalBiogerontology
Volume8
Issue number2
DOIs
Publication statusPublished - Apr 2007

Keywords

  • AAT
  • AMI
  • Centenarians
  • Longevity
  • Serine-protease inhibitor (Pi)

ASJC Scopus subject areas

  • Geriatrics and Gerontology

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    Listì, F., Candore, G., Grimaldi, M. P., Lio, D., Colonna-Romano, G., Orlando, V., Caruso, M., Hoffmann, E., Paolisso, G., Franceschi, C., & Caruso, C. (2007). Alpha1-antitrypsin heterozygosity plays a positive role in attainment of longevity. Biogerontology, 8(2), 139-145. https://doi.org/10.1007/s10522-006-9041-y