| Objective: Asthma is a pulmonary disease characterized by chronic inflammation of the airways and bronchial hyperresponsiveness. The findings of previous epidemiologic studies suggest that asthma is a multifactorial disease influenced by both genetic and environmental factors.Although the nature of the genetic factors remains unknown, it has become evident that the airway narrowing in asthma is a consequence of a special type of chronic inflammation of the airway wall. Among the mediators implicated in the genesis of this inflammatory process, bradykinin > tachykinin and substance P are considered to play important roles in the pathogenesis of asthma, especially in neurogenic inflammation. Bradykinin causes bronchoconstrictionN enhances vascular permeability, leads to mucosal oedema, and increases the production of mucus by direct effects or stimulating release of neuropeptides, such as tachykinins from C-fibres. Bradykinin and substance P,which have profound inflammatory effects, are inactived, at least in part, by angiotensin converting enzyme (ACE) . In addition to theinactivation of bradykinin and tachykinin peptides, the other major function of ACE is the conversion of angiotensin I into angiotensin II (A II), a compound that may also be involved in the pathogenesis of asthma by interacting with airway smooth muscle. A number of investigators have reported that ACE inhibitors increase the bronchial responsiveness of patients with asthma. Furthermore , it is well known that they often cause non-productive coughing as a side-effect, possibly due to bradykinin influence on the airways. Thus changes in the enzyme may play a role in asthma pathogenesis. It has recently been shown that the ACE gene contains a polymorphism based on the presence [insertion (I)] or absence [deletion (D)] of a nonsense DNA fragment. The polymorphism is located in intron 16 , so the ACE itself does not differ due to the genotypic variation, but the polymophism accounts for 47% of the total phenotypic variance in serum ACE levels. There are three genotypes: deletion homozygotes, DD;insertion homozygotes, II; and heterozygotes, DI. The serum ACE level with the DD type is reported to be about double that of the II type and that of the DI type is intermediate. Because ACE is heavily expressed in the lungs and plays a key role in the metabolism of peptides possibly involved in the pathogenesis of asthma, we asked whether the polymorphism of the ACE gene could be implicated as oneof the genetic factors in patients with asthma. Thus the aim of this study was to test the hypothesis of an association between the insertion/deletion polymorphism of the ACE gene and asthma in an adult population.Methods: Forty-nine consecutive patients with asthma (30 men and 19 women), aged 14-63 years were studied. Patients were evaluated in the outpatient clinic for chronic asthma or in the hospitalization unit for acute exacerbation of asthma. Asthma was diagnosed according to the national official statement which was established in 1997.Eighty-five healthy subjects (49 men and 36 women), aged 20-66 years ,who were free of lung disease and had no clinical evidence of personal or familial atopy or asthma were recruited from the medical staff and served as control subjects. Patients and control subjects with clinical evidence of cardiovascular disease^ diabetic nephropathy and sarcoidosis were excluded because of the possible assciation between the insertion/delection polymorphism of the ACE gene and these diseases. Determination of ACE genotypes: Genomic DNA was prepared from frozen peripheral blood by using standard procedures, and the D and I alleles were identified, on the basis of polymerase-chain-reaction(PCR)amplification of the respective fragments of the ACE gene. PCR products were separated by agarose gel electrophoresis, and DNA was visualized by ethidium bromide staining. Subjects werethen classified, according to the absence or presence of the 287 bp insertion in intron 16 of the ACE gene, as DD or II homozygotes or as ID heter...
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