Centro di Riferimento Regionale per il Deficit di Alfa1-Antitripsina, Prima Divisione di Medicina Interna, Spedali Civili, Cattedra di Malattie dell'Apparato Respiratorio, Università di Brescia, Brescia, Italy.
Respiration. 2011;82(5):418-25. doi: 10.1159/000325067. Epub 2011 Apr 6.
Current guidelines for α1-antitrypsin deficiency (AATD) state that adult population screening should only be done in high-risk areas. Up-to-date genetic methods are always recommended.
To determine the prevalence of AATD in a suspected high-risk area by population screening, applying new genetic analyses and comparing the prevalence of liver and lung abnormalities in subjects with or without AATD.
Adult residents of Pezzaze, a village in an Italian alpine valley, voluntarily participated in the screening, and were examined for: nephelometric α1-antitrypsin (AAT) serum level, DNA analysis (mutagenic polymerase chain reaction and restriction fragment length polymorphism tests for Z and S AATD causative mutations, and denaturing high-performance liquid chromatography and/or direct gene sequencing if needed), serum aspartate and alanine transaminases, a respiratory questionnaire and the Medical Research Council dyspnea index scale. The prevalence of AATD was compared with that expected in Italy (Hardy-Weinberg equilibrium), and transaminases and the prevalence of respiratory symptoms were compared between study groups.
Of 1,353 residents, 817 (60.4%) participated; 67 (8.2%) had low AAT serum levels (<90 mg/dl); 118 were carriers of AATD-associated alleles, 4 (0.5%) homozygotes or compound heterozygotes (1 Z, 1 S, 2 ZP(brescia)), 114 (14%) heterozygotes (46 Z, 52 S, 9 P(brescia), 4 M(wurzburg), 2 I, 1 P(lowell)). The prevalence and frequency of all AATD-related alleles was higher than expected for Italy (p < 0.001). There were no differences in symptoms of respiratory disease and transaminases between individuals with normal and low serum AAT.
The screening design is one of the main strengths of this study. The large number of mostly asymptomatic individuals with AATD identified suggests that in high-risk areas adult population screening programs employing the latest genetic methods are feasible. Early recognition of individuals at risk means primary or secondary prevention measures can be taken.
目前的α1-抗胰蛋白酶缺乏症（AATD）指南指出，仅在高危地区进行成人人群筛查。始终建议使用最新的遗传方法。
通过人群筛查确定疑似高危地区的 AATD 患病率，应用新的遗传分析方法，并比较 AATD 患者与无 AATD 患者的肝脏和肺部异常患病率。
意大利阿尔卑斯山谷 Pezzaze 村的成年居民自愿参加筛查，检查内容包括：血清α1-抗胰蛋白酶（AAT）的光散射测定法、DNA 分析（突变聚合酶链反应和限制性片段长度多态性检测 Z 和 S AATD 致病突变，必要时进行变性高效液相色谱和/或直接基因测序）、血清天冬氨酸转氨酶和丙氨酸转氨酶、呼吸问卷和医学研究委员会呼吸困难指数量表。将 AATD 的患病率与意大利的预期患病率（哈迪-温伯格平衡）进行比较，并比较研究组之间的转氨酶和呼吸症状患病率。
在 1353 名居民中，有 817 名（60.4%）参加了筛查；67 名（8.2%）血清 AAT 水平较低（<90mg/dl）；118 名是 AATD 相关等位基因携带者，其中 4 名（0.5%）为纯合子或复合杂合子（1 个 Z，1 个 S，2 个 ZP（brescia）），114 名（14%）为杂合子（46 个 Z，52 个 S，9 个 P（brescia），4 个 M（wurzburg），2 个 I，1 个 P（lowell））。所有与 AATD 相关的等位基因的患病率和频率均高于意大利的预期值（p<0.001）。血清 AAT 正常和较低的个体之间，呼吸疾病症状和转氨酶无差异。
筛查设计是本研究的主要优势之一。发现大量无症状的 AATD 个体，表明在高危地区，采用最新遗传方法的成人人群筛查方案是可行的。早期识别高危人群意味着可以采取一级或二级预防措施。
