Identification of a rare p.G320R alpha-1-antitrypsin variant in emphysema and lung cancer patients

Genetics and Molecular Biology

Mila Ljujic¹  Aleksandra Topic²  Aleksandra Nikolic¹  Aleksandra Divac¹  Milan Grujic²  Marija Mitic-milikic²  Dragica Radojkovic¹ 

[1] ,Institute of Molecular Genetics and Genetic EngineeringBelgrade,Serbia

关键词: alpha-1-antitrypsin;    emphysema;    lung cancer;    P variant;    specific trypsin inhibitory activity;   

DOI  :  10.1590/S1415-47572009005000100

来源: SciELO

【 摘 要 】

The alpha-1-antitrypsin (A1AT) gene is highly polymorphic, with more than 100 genetic variants identified of which some can affect A1AT protein concentration and/or function and lead to pulmonary and/or liver disease. This study reports on the characterization of a p.G320R variant found in two patients, one with emphysema and the other with lung cancer. This variant results from a single base-pair substitution in exon 4 of the A1AT gene, and has been characterized as P by isoelectric focusing. Functional evaluation of the A1AT p.G320R variant was through comparing specific trypsin inhibitory activity in two patients with pulmonary disorders, carriers of the p.G320R variant, and 19 healthy individuals, carriers of normal A1AT M variants. Results showed that specific trypsin inhibitory activity was lower in both emphysema (2.45 mU/g) and lung cancer (2.07 mU/g) patients than in carriers of the normal variants (range 2.51-3.71 mU/g). This rare A1AT variant is associated with reduced functional activity of A1AT protein. Considering that it was found in patients with severe pulmonary disorders, this variant could be of clinical significance.

【 授权许可】

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