Involvement of genetic polymorphisms in arterial hypertension has already been reported, including GST genes, with contrasting results. The present research evaluates the possible association between GST gene polymorphisms and essential hypertension (EH) in an Italian population sample. 193 hypertensive subjects and 210 healthy controls were recruited. Buccal cells were collected from each subject using an oral swab and DNA was extracted using the phenol:chloroform:isoamilic alcohol method. GST SNPs were determined using the PCR-RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. Among GST polymorphisms, only the frequency of the GSTT1 null phenotype was significantly higher in hypertensive patients than in normotensive participants. GSTT1 null individuals were significantly associated with increased risk of hypertension [P < 0.001; adjusted OR 2.24 (1.43-3.50)]. In sex-based analysis, the risk was significantly higher in female hypertensives [P < 0.001; adjusted OR 3.25 (1.78-5.95)] but not in male subjects. This study analyzed all GST gene that, in other research, have been studied in relation to arterial hypertension and the GSTO polymorphisms, showing an association only with GSTT1. The results for the GSTO genes represent the first analysis of this GST class in relation to blood pressure regulation. The association between the GSTT1 null phenotype and EH was confirmed in the overall population and in women, but not in men. These data suggest that GSTT1 could be a sex-specific candidate gene for EH.
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.
Our studies confirm the lack of association between GSTO1 variants and EH risk, also for two uncommon genetic variants with large functional effects. However, our study highlighted some hypotheses (sex-specific marker, antioxidant function, arsenic metabolism, and modulation of inflammation processes) that might help to clarify the potential role of GSTO1 in EH pathophysiology.
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