Angiotensin-converting enzyme I/D polymorphism in Behçet's disease

Objective: To investigate a potential relationship between I/D polymorphism within intron 16 of the angiotensin-converting enzyme (ACE) gene located on human chromosome 17 and Behçet's disease. Materials and Methods: Genomic DNA was obtained from 35 Turkish patients diagnosed with Behçet's disease according to the International Study Group criteria and 150 healthy individuals. Polymerase chain reaction was used to detect the presence of I and D (insertion and deletion) alleles in intron 16 of the ACE gene in these DNA samples. Results: We found differences in ACE I/D polymorphism between Behçet's disease and healthy controls (χ2 = 4.61, d.f. = 1, p = 0.044). In Behçet's disease patients, the D allele frequency was 84.3% and I allele frequency 15.7%. Conclusion: An association between Behçet's disease and ACE polymorphism may provide a useful basis for future molecular studies and therapeutic approaches in this complex disease. Copyright © 2005 S. Karger AG

Association studies for asthma and atopic diseases: a comprehensive review of the literature

Hundreds of genetic association studies on asthma-related phenotypes have been conducted in different populations. To date, variants in 64 genes have been reported to be associated with asthma or related traits in at least one study. Of these, 33 associations were replicated in a second study, 9 associations were not replicated either in a second study or a second sample in the same study, and 22 associations were reported in just a single published study. These results suggest the potential for a great amount of heterogeneity underlying asthma. However, many of these studies are methodologically limited and their interpretation hampered by small sample sizes

Endothelin-1 and the use of induced sputum to investigate its role in airway diseases

Endothelin (ET)-1 is a 21-amino acid peptide which has been the subject of intense interest since its discovery in 1988. It has a number of properties which may be important in physiology and pathophysiology, including potential relevance to airway diseases. A putative role for ET-1 in asthma has been proposed, and we sought to examine this further, as well as to extend our investigations to other respiratory diseases, including chronic obstructive pulmonary disease and cystic fibrosis. The technique of sputum induction has been developed recently as a non-invasive method of obtaining airway secretions for analysis, and we have applied this to the investigation of the role of ET-1 in diseases involving the airway. We have demonstrated for the first time that ET-1 is a highly potent bronchoconstrictor with a prolonged duration of action when administered by aerosol in asthma, and that asthmatics exhibit bronchial hyperreactivity to ET-1 compared with non-asthmatic subjects, but we found no evidence of an acute inflammatory airway response at 30 minutes or 4 hours following ET-l-induced bronchoconstriction in asthma, assessed by analysis of cell counts and soluble mediators in induced sputum. The bronchoconstrictor activity of ET-1 was not potentiated by an infusion of angiotensin II in stable asthmatics, despite animal evidence of potentiation, although the possibility of such interaction remains in acute severe asthma, where plasma angiotensin II levels are elevated. We did not find increased levels of ET-1 in induced sputum in mild asthmatics compared with non-asthmatic subjects, nor was there a fall in sputum ET-1 comparing samples obtained during acute severe asthma with those obtained in convalescence, although sputum and saliva levels of ET-1 are greater than plasma ET-1, suggesting local production within the respiratory tract. Examination of sputum ET-1 following allergen challenge in asthma showed a trend towards an increase in sputum ET-1 after allergen challenge, with a relationship between the increase in sputum ET-1 and the extent of sputum eosinophilia, suggesting a relationship between asthmatic airway inflammation and ET- 1 release. Sputum ET-1 is increased in smokers without lung disease, and in subjects with chronic obstructive pulmonary disease (COPD), with a trend towards a fall in sputum ET-1 comparing acute exacerbation with convalescence. Finally, we have demonstrated a marked increase in sputum ET-1 in patients with cystic fibrosis compared with healthy subjects. We conclude from this series of studies that there is continuing evidence for a role for ET-1 in a number of diseases affecting the airway, and speculate that drugs which oppose the action of ET-1 may have a role in the treatment of these conditions