Listì Florinda, Candore Giuseppina, Grimaldi Maria Paola, Lio Domenico, Colonna-Romano Giuseppina, Orlando Valentina, Caruso Marco, Hoffmann Enrico, Paolisso Giuseppe, Franceschi Claudio, Caruso Calogero
Dipartimento di Biopatologia e Metodologie Biomediche, Gruppo di Studio sull'Immunosenescenza, Corso Tukory 211, Palermo 90134, Italy.
Biogerontology. 2007 Apr;8(2):139-45. doi: 10.1007/s10522-006-9041-y. Epub 2006 Sep 20.
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.
参与心血管疾病（CVD）的基因在人类长寿方面发挥着相反的作用。α1-抗胰蛋白酶（AAT）是一种丝氨酸蛋白酶抑制剂，可防止中性粒细胞弹性蛋白酶对组织造成蛋白水解损伤。AAT在心血管疾病中的作用尚未得到明确评估，其对长寿的影响也尚未得到充分研究。为了阐明这些问题，我们研究了AAT等位基因变体在3个队列中的分布情况：127名患有急性心肌梗死（AMI）的年轻患者、255名年轻对照者以及143名来自西西里岛的百岁老人。Z等位基因频率在百岁老人中最为常见（13.3%），在健康年轻对照者中处于中间水平（3.1%），而在AMI患者中频率较低（1.2%）（P = 0.0000001）。杂合子MZ基因型在百岁老人中显著过度代表（38/143），在AMI患者中则代表不足（3/127），在年轻对照者中处于中间值（16/255）（P = 0.0000001）。在对公认的AMI危险因素进行调整后，MZ基因型在西西里人群中仍然是发生AMI的显著负性危险因素。因此，我们的数据表明MZ杂合性在成功衰老方面具有积极作用，这与该基因型对心血管缺血性疾病的积极影响有关。
