Wiesemann Gayle S, Oshins Regina A, Flagg Tammy O, Brantly Mark L
University of Florida College of Medicine, Gainesville, Florida, United States.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, Florida, United States.
Chronic Obstr Pulm Dis. 2023 Jan 25;10(1):7-21. doi: 10.15326/jcopdf.2022.0321.
The gene encodes the serine protease inhibitor alpha-1 antitrypsin (AAT) and is located on chromosome 14q31-32.3 in a cluster of homologous genes likely formed by exon duplication. AAT has a variety of anti-inflammatory properties. Its clinical relevance is best illustrated by the genetic disease alpha-1 antitrypsin deficiency (AATD) which is associated with an increased risk for chronic obstructive pulmonary disease (COPD) and cirrhosis. While 2 single nucleotide polymorphisms (SNPs) , S and Z, are responsible for more than 95% of all individuals with AATD, there are a number of rare variants associated with deficiency and dysfunction, as well as those associated with normal levels and function. Our laboratory has identified a number of novel AAT alleles that we report in this manuscript. We screened more than 500,000 individuals for AATD alleles through our testing program over the past 20 years. The characterization of these alleles was accomplished by DNA sequencing, measurement of AAT plasma levels and isoelectric focusing at pH 4-5. We report 22 novel AAT alleles discovered through our screening programs, such as Z and QO, and review the current literature of known AAT genetic variants.
该基因编码丝氨酸蛋白酶抑制剂α-1抗胰蛋白酶（AAT），位于14号染色体q31 - 32.3上，处于一个可能由外显子重复形成的同源基因簇中。AAT具有多种抗炎特性。其临床相关性在α-1抗胰蛋白酶缺乏症（AATD）这一遗传疾病中得到了最好的体现，该疾病与慢性阻塞性肺疾病（COPD）和肝硬化风险增加相关。虽然2个单核苷酸多态性（SNP），即S和Z，导致了超过95%的AATD个体，但也存在一些与缺乏和功能障碍相关的罕见变异，以及与正常水平和功能相关的变异。我们实验室在本手稿中报告了一些新发现的AAT等位基因。在过去20年里，我们通过检测项目对超过50万人进行了AATD等位基因筛查。这些等位基因的特征通过DNA测序、AAT血浆水平测量以及pH 4 - 5条件下的等电聚焦来确定。我们报告了通过筛查项目发现的22个新的AAT等位基因，如Z和QO，并综述了已知AAT基因变异的当前文献。
