Lack of association between GSTM1, GSTP1, and GSTT1 gene polymorphisms and asthma in adult patients from Rome, central Italy.

BACKGROUND: Asthma is a complex multifactorial disease that is not yet fully understood. Oxidative stress due to an imbalance between the oxidative forces and the antioxidant defense systems has been implicated in asthma pathogenesis. However, much debate still surrounds the key genetic factors involved in the development of this disease. Candidate genes include the glutathione S-transferases (GSTs). In particular, mu, pi, and theta classes of GSTs play an important role in regulating inflammatory responses. However, few and contradictory data are available on the association between asthma development and GST gene polymorphisms (GSTM1, GSTP1, and GST1). OBJECTIVE: To investigate whether GSTM1, GSTT1, and GSTP1 polymorphisms are associated with asthma development. METHODS: We recruited 200 unrelated healthy individuals and 199 asthmatic patients from Rome in Central Italy. Genotyping of GSTMI and GSTT1 genes was performed by a multiplex polymerase chain reaction (PCR) while the GSTP1 polymorphism (rs1695) was determined using PCR-restriction fragment length polymorphism analysis. RESULTS: Our results suggest that the GST polymorphisms analyzed are not associated with asthma, confirming the uncertain role of GST genes in the development of asthma. CONCLUSIONS: Oxidative stress is certainly involved in the development of asthma, and GSTs may therefore influence asthma risk, although, as our results show, their role in pathogenesis remains to be elucidated. Future studies should focus on the interactions of GST genes with the environment and other antioxidant genes to shed light on the role of GSTs in asthma.

Glutathione S-transferase gene polymorphisms and air pollution as interactive risk factors for asthma in a multicentre Italian field study: A preliminary study.

BACKGROUND: Asthma is one of the most common chronic diseases. Several studies have indicated that oxidative stress impairs pulmonary function. Glutathione S-transferases (GSTs) are believed to be critical in the protection of cells from reactive oxygen species. AIM: In this case-control study we analysed the possible association between polymorphism in several cytosolic GST genes, air pollution and asthma development. METHODS: Genotyping of GSTM1 and GSTT1 genes was carried out by a multiplex PCR; GSTA1, GSTO1, GSTO2, GSTP1 polymorphisms were determined using the PCR-RFLP method. Data on atmospheric pollutants were collected by the regional air-quality monitoring network. RESULTS: Among all the polymorphisms studied, the frequencies of GSTA1, GSTM1, GSTO2 and GSTT1 genotypes found in the group of asthmatic patients seem to differ from the frequencies of those found in the control group. Air pollutants were analysed and the air quality parameters considered proved to be significantly different, and therefore suitable for this study. CONCLUSION: The final result of this research should hopefully lead to a better understanding of gene-environment interactions, so allowing earlier prediction and diagnosis of asthma disease and providing an efficient means of prevention.

Esophageal dysmotility and gastroesophageal reflux in intrinsic asthma.

This study was undertaken to determine the prevalence of esophageal motor abnormalities, the incidence of gastroesophageal reflux, and the coexistence of gastroesophageal reflux with esophageal dysmotility in patients with intrinsic asthma. Based on clinical criteria, 34 consecutive asthmatics, 15 patients with gastroesophageal reflux, and 10 subjects with upper gastrointestinal symptoms with normal results of esophageal manometry and 24-hr esophageal pH test (controls) were studied. Esophageal motor disorders were noted in 23 of 34 asthmatics, and in 10 of 15 patients with acid reflux but in none of the subjects of the control group. A positive result of the prolonged esophageal pH study (pH in the distal esophagus less than 4 for more than 4.2% of the recording time) was obtained in 14 of 17 patients with asthma (only 17 of the original patients were tested because the others did not give informed consence for this test) and in all patients with gastroesophageal reflux. None of the members of the control group had positive test results. The findings of this study show that: (1) it is possible to identify a group of subjects with nonallergic asthma presenting with esophageal dysmotility, (2) the 24-hr esophageal pH study must be properly done in such patients; (3) esophageal motor abnormalities are often associated with positive pH results; and (4) more reflux was observed while in a supine position (especially during the night) than that observed either in control or reflux patients. Based on these results, patients with intrinsic asthma with reflux can benefit from both acid suppressive and prokinetic drugs with notable clinical implications regarding standard treatment for asthma, and those with prevalent supine compared to upright reflux could even benefit from surgery.

Quality of life of COPD patients treated by long-term oxygen.

The three main dimensions of quality of life (physical function, social activities, and psychological status) were evaluated by a questionnaire in 41 COPD patients with severe respiratory failure treated by long-term oxygen. The results were compared with those obtained in patients suffering from COPD without chronic respiratory failure and in patients suffering from severe diabetes and/or atherosclerosis. A relevant impairment of the indexes of quality of life was found in the group of subjects with chronic respiratory failure. The extent of the impairment was significantly higher in these subjects than in the two other groups of patients.