Clinic of Children's Diseases, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Santariskiu Str. 7, LT-08410 Vilnius, Lithuania.
Department of Genetics and Clinical Immunology, National Institute of Tuberculosis and Lung Diseases, 01-138 Warsaw, Poland.
Adv Respir Med. 2024 Aug 5;92(4):291-299. doi: 10.3390/arm92040028.
Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (PiSZ, PiMZ, PiMS) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the PiS allele incidence was 2.07% (3 cases) and the PiZ allele was 6.9% (10 cases). The PiZ allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: PiS 10.3% vs. 15.8% and PiZ 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.
严重遗传性α-1 抗胰蛋白酶缺乏症（AATD）是一种常染色体遗传疾病，与慢性阻塞性肺疾病（COPD）有关。杂合子、轻度缺乏变体（PiSZ、PiMZ、PiMS）的意义不太清楚。我们研究了 145 名患有评估严重程度的喘息儿童（最大 72 个月）的 AATD 基因型，使用小儿呼吸评估措施（BCCH PRAM 评分）。包括 74 名无气道阻塞的对照组儿童。使用散射比浊法和实时 PCR 从干血斑样本中测定 AAT 浓度和 Pi 表型；通过等电聚焦鉴定 PiS 和 PiZ 等位基因。在喘息者中，PiS 等位基因的发生率为 2.07%（3 例），PiZ 等位基因的发生率为 6.9%（10 例）。与对照组相比，喘息者中 PiZ 等位基因的频率更高（44.8%比 20.27%）和立陶宛普通人群（44.8%比 13.6%），与立陶宛成年 COPD 患者相似：PiS 为 10.3%比 15.8%，PiZ 为 44.8%比 46.1%。未发现 AAT 基因型与喘息严重程度之间存在关联。喘息儿童的 Z和 S*等位基因频率与成年 COPD 患者相似的发现表明，存在一种潜在的遗传易感性，将儿童早期喘息与成年期 COPD 的发展联系起来。需要更大的队列研究来证实这一发现。
