alpha 1-antitrypsin TAQ I polymorphism and alpha 1-antichymotrypsin mutations in patients with obstructive pulmonary disease

• Published in: Respiratory medicine 1999-09, Vol.93 (9), p.648-654
• Main Authors: Benetazzo, M G, Gilè, L S, Bombieri, C, Malerba, G, Massobrio, M, Pignatti, P F, Luisetti, M
• Format: Article
• Language: English
• Subjects: Aged; alpha 1-Antichymotrypsin - genetics; alpha 1-Antitrypsin - genetics; Case-Control Studies; Female; Humans; Italy; Lung Diseases, Obstructive - genetics; Male; Middle Aged; Polymorphism, Genetic; Risk Factors
• ISSN: 0954-6111

Obstructive pulmonary disease is a multifactorial condition deriving from the interaction of environmental and genetic factors. From biochemical knowledge of the basis of the disease, alpha 1-antitrypsin and alpha 1-antichymotrypsin are considered two likely candidate genes. We therefore designed an association study comprising 232 unrelated Italian individuals divided as follows: 89 individuals with obstructive lung disease (66 with COPD and 23 with disseminated bronchiectasis) and 143 controls (45 patients with non-obstructive lung disease and 98 healthy individuals). We screened for Taq I (G1237A) polymorphism of the alpha 1-antitrypsin gene as well as the rare variants Bonn-1 (Pro229Ala), Bochum-1 (Leu55Pro), Isehara-1 (Met389Val) and Isehara-2 (1258delAA), and the common signal peptide polymorphism Thr-15Ala of the alpha 1-antichymotrypsin gene. The frequencies of Taq I G1237A alleles were 11.7 and 10.8% in obstructed patients and controls, respectively (P = 0.43), while those of signal peptide Thr-15Ala alleles were 51.6 and 50.3% in obstructed patients and controls, respectively (P = 0.42). We conclude that alpha 1-antitrypsin Taq I polymorphism and alpha 1-antichymotrypsin Thr-15Ala mutation are not major genetic risk factors for the development of obstructive lung disease in Italian patients. The alpha 1-antichymotrypsin rare variants were not detected: our results do not exclude the possibility that other alpha 1-antichymotrypsin gene mutations might be present in Italian obstructed patients but, if so, these genetic defects must be rare.