α1-Antitrypsin TAQ I polymorphism and α1-antichymotrypsin mutations in patients with obstructive pulmonary disease

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, α1-antitrypsin and α1-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 α1-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 α1-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 α1-antitrypsin Taq I polymorphism and α1-antichymotrypsin Thr-15Ala mutation are not major genetic risk factors for the development of obstructive lung disease in Italian patients. The α1-antichymotrypsin rare variants were not detected: our results do not exclude the possibility that other α1-antichymotrypsin gene mutations might be present in Italian obstructed patients but, if so, these genetic defects must be rare.