Polymorphism of angiotensin-converting enzyme gene and genetic susceptibility to asthma with familial aggregation.

OBJECTIVE

Angiotensin-converting enzyme (ACE) plays a key role in the metabolism of angiotensin II (AT II) and inactivation of bradykinins and tachykinins, which are potent bronchialconstrictors and mediators of inflammation asthma, and ACE is heavily expressed in the lungs. An insertion-deletion (D/I) polymorphism of ACE gene has been shown to be associated with levels of ACE. We investigate whether the polymorphism of ACE gene is associated with asthma and bronchial responsiveness.

METHODS

A case-control study was carried out in 50 asthmatics, 7 families with at least 2 asthmatic individuals, and 50 healthy subjects. The insertion/deletion (I/D) polymorphism of ACE gene was amplified by polymerase chain reaction (PCR). Methacholine brocho-provocation and pulmonary function tests were performed in all asthmatics. RESULTS. There was an higher gene frequency of DD genotype of ACE gene in asthmatic subjects and families individuals compared with healthy subjects (46%, 53% vs 16%, P<0.05; odd ratio 4.98). An- higher prevalence of DD genotype of ACE was in patients with bronchial hyperresposiveness (BHR) (67% vs 33%, P<0.05; odd ratio 3.8). Accordingly, the mean values of FEV1% and FEV1/FVC were higher in asthmatics carrying non-DD alleles than patients with DD genotype (73.78% vs 56.56%, P<0.05, 79.19% vs 69.29%, P<0.05, respectively).

CONCLUSION

These results suggested that DD allele of ACE genotype was significantly involved in genetic susceptibility to asthma. DD genotype of ACE might be a risk factor for the degree of airway obstruction, it could also be implicated in pathogenesis of bronchial hyperresponsiveness.