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

Obstructive pulmonary disease is a multifactorial condition deriving from t he interaction of environmental and genetic factors. From biochemical knowl edge of the basis of the disease, alpha 1-antitrypsin and alpha 1-antichymo trypsin 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-ob structive lung disease and 98 healthy individuals). We screened for Taq I ( C1237A) polymorphism of the alpha 1-antitrypsin gene as well as the rare va riants Bonn-1 (Pwro229Ala), Bochum -1 (Leu55Pro), Isehara-1 (Met389Val) and Isehara-2 (1258delAA), and the common signal peptide polymorphism Thr-15Al a of the alpha 1-antichymotrypsin gene. The frequencies of Taq I G1237A all eles 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 5 0.3% in obstructed patients and controls, respectively (P = 0.42). We concl ude that alpha 1-antitrypsin Taq I polymorphism and alpha 1-antichymotrypsi n Thr-15Ala mutation are not major genetic risk factors for the development of obstructive lung disease in Italian patients. The alpha 1-antichymotryp sin rare variants were not detected: our results do not exclude the possibi lity that other alpha 1-antichymotrypsin gene mutations might be present in Italian obstructed patients but, if so, these genetic defects must be rare . (C) 1999 HARCOURT PUBLISHERS LTD.