Real-world use of remdesivir for the treatment of patients admitted to Italian hospitals with COVID-19: the nationwide retrospective FADOI-RECOVER study.

BACKGROUND: Remdesivir is widely used for treatment of SARS-CoV-2 pneumonia. The aim of this study was to evaluate the characteristics of patients with moderate-to-severe COVID-19 treated with remdesivir, and their outcomes during hospitalization. METHODS: This retrospective observational multicenter study included consecutive patients, hospitalized for moderate-to-severe COVID-19 (September 2020-September 2021), who were treated with remdesivir. RESULTS: One thousand four patients were enrolled, all with onset of symptoms occurring less than 10 days before starting remdesivir; 17% of patients had 4 or more concomitant diseases. Remdesivir was well tolerated, adverse drug reactions (ADRs) being reported in 2.3% of patients. In-hospital death occurred in 80 patients (8.0%). The median timing of the first remdesivir dose was 5 days after symptom onset. The following endpoints did not differ according to the time span from the onset of symptoms to the first dose: length of hospitalization, in-hospital death, composite outcome (in-hospital death and/or endotracheal intubation). Advanced age, number of comorbidities ≥ 4, and severity of respiratory failure at admission were associated with poor in-hospital outcomes. CONCLUSION: In a real-world setting, remdesivir proved to be a safe and well-tolerated treatment for moderate-to-severe COVID-19. In patients receiving remdesivir less than 3 or 5 days from the onset of SARS-CoV-2 symptoms, mortality and the need for mechanical ventilation did not differ from the rest of the sample.

LDL-cholesterol control in the primary prevention of cardiovascular diseases: An expert opinion for clinicians and health professionals.

AIMS: Although adequate clinical management of patients with hypercholesterolemia without a history of known cardiovascular disease is essential for prevention, these subjects are often disregarded. Furthermore, the scientific literature on primary cardiovascular prevention is not as rich as that on secondary prevention; finally, physicians often lack adequate tools for the effective management of subjects in primary prevention and have to face some unsolved relevant issues. This document aims to discuss and review the evidence available on this topic and provide practical guidance. DATA SYNTHESIS: Available algorithms and risk charts represent the main tool for the assessment of cardiovascular risk in patients in primary prevention. The accuracy of such an estimate can be substantially improved considering the potential contribution of some additional risk factors (C-reactive protein, lipoprotein(a), family history of cardiovascular disease) and conditions (environmental pollution, sleep quality, socioeconomic status, educational level) whose impact on the cardiovascular risk has been better understood in recent years. The availability of non-invasive procedures to evaluate subclinical atherosclerosis may help to identify subjects needing an earlier intervention. Unveiling the presence of these conditions will improve cardiovascular risk estimation, granting a more appropriate intervention. CONCLUSIONS: The accurate assessment of cardiovascular risk in subjects in primary prevention with the use of algorithms and risk charts together with the evaluation of additional factors will allow physicians to approach each patient with personalized strategies, which should translate into an increased adherence to therapy and, as a consequence, a reduced cardiovascular risk.

Intra- and Extra-Hospitalization Monitoring of Vital Signs-Two Sides of the Same Coin: Perspectives from LIMS and Greenline-HT Study Operators.

BACKGROUND: In recent years, due to the epidemiological transition, the burden of very complex patients in hospital wards has increased. Telemedicine usage appears to be a potential high-impact factor in helping with patient management, allowing hospital personnel to assess conditions in out-of-hospital scenarios. METHODS: To investigate the management of chronic patients during both hospitalization for disease and discharge, randomized studies (LIMS and Greenline-HT) are ongoing in the Internal Medicine Unit at ASL Roma 6 Castelli Hospital. The study endpoints are clinical outcomes (from a patient's perspective). In this perspective paper, the main findings of these studies, from the operators' point of view, are reported. Operator opinions were collected from structured and unstructured surveys conducted among the staff involved, and their main themes are reported in a narrative manner. RESULTS: Telemonitoring appears to be linked to a reduction in side-events and side-effects, which represent some of most commons risk factors for re-hospitalization and for delayed discharge during hospitalization. The main perceived advantages are increased patient safety and the quick response in case of emergency. The main disadvantages are believed to be related to low patient compliance and an infrastructural lack of optimization. CONCLUSIONS: The evidence of wireless monitoring studies, combined with the analysis of activity data, suggests the need for a model of patient management that envisages an increase in the territory of structures capable of offering patients subacute care (the possibility of antibiotic treatments, blood transfusions, infusion support, and pain therapy) for the timely management of chronic patients in the terminal phase, for which treatment in acute wards must be guaranteed only for a limited time for the management of the acute phase of their diseases.

Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancerassociated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60- 89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: NCT03045406.

Acute cardiovascular events in patients with community acquired pneumonia: results from the observational prospective FADOI-ICECAP study.

BACKGROUND: The burden of cardiovascular (CV) complications in patients hospitalised for community-acquired pneumonia (CAP) is still uncertain. Available studies used different designs and different criteria to define CV complications. We assessed the cumulative incidence of acute of CV complications during hospitalisation for CAP in Internal Medicine Units (IMUs). METHODS: This was a prospective study carried out in 26 IMUs, enrolling patients consecutively hospitalised for CAP. Defined CV complications were: newly diagnosed heart failure, acute coronary syndrome, new onset of supraventricular or ventricular arrhythmias, new onset hemorrhagic or ischemic stroke or transient ischemic attack. Outcome measures were: in-hospital and 30-day mortality, length of hospital stay and rate of 30-day re-hospitalisation. RESULTS: A total of 1266 patients were enrolled, of these 23.8% experienced at least a CV event, the majority (15.5%) represented by newly diagnosed decompensated heart failure, and 75% occurring within 3 days. Female gender, a history of CV disease, and more severe pneumonia were predictors of CV events. In-hospital (12.2% vs 4.7%, p < 0.0001) and 30-day (16.3% vs 8.9%, p = 0.0001) mortality was higher in patients with CV events, as well as the re-hospitalisation rate (13.3% vs 9.3%, p = 0.002), and mean hospital stay was 11.4 ± 6.9 vs 9.5 ± 5.6 days (p < 0.0001). The occurrence of CV events during hospitalisation significantly increased the risk of 30-day mortality (HR 1.69, 95% CI 1.14-2.51; p = 0.009). CONCLUSION: Cardiovascular events are frequent in CAP, and their occurrence adversely affects outcome. A strict monitoring might be useful to intercept in-hospital CV complications for those patients with higher risk profile. TRIAL REGISTRATION: NCT03798457 Registered 10 January 2019 - Retrospectively registered.

Phenome-wide association study of TTR and RBP4 genes in 361,194 individuals reveals novel insights in the genetics of hereditary and wildtype transthyretin amyloidoses.

Transthyretin (TTR) gene has a causal role in a hereditary form of amyloidosis (ATTRm) and is potentially involved in the risk of wild-type transthyretin amyloidosis (ATTRwt). To understand the genetics of ATTRm and ATTRwt, we conducted a phenome-wide association study of TTR gene in 361,194 participants of European descent testing coding and non-coding variants. Among the 382 clinically relevant phenotypes tested, TTR non-coding variants were associated with 26 phenotypic traits after multiple testing correction. These included signs related to both ATTRm and ATTRwt such as chronic ischaemic heart disease (rs140226130, p = 2.00 × 10-6), heart failure (rs73956431, p = 2.74 × 10-6), atrial fibrillation (rs10163755, p = 4.63 × 10-6), dysphagia (rs2949506, p = 3.95 × 10-6), intestine diseases (rs970866, p = 7.14 × 10-6) and anxiety (rs554521234, p = 8.85 × 10-6). Consistent results were observed for TTR disease-causing mutation Val122Ile (rs76992529) with respect to carpal tunnel syndrome (p = 6.41 × 10-6) and mononeuropathies of upper limbs (p = 1.22 × 10-5). Sex differences were also observed in line with ATTRm and ATTRwt epidemiology. Additionally, we explored possible modifier genes related to TTR function, observing convergent associations of RBP4 variants with the clinical phenotypes associated with TTR locus. In conclusion, we provide novel insights regarding the molecular basis of ATTRm and ATTRwt based on large-scale cohort, expanding our understanding of the phenotypic spectrum associated with TTR gene variation.

What Quality and Safety of Care for Patients Admitted to Clinically Inappropriate Wards: a Systematic Review.

BACKGROUND: In countries with public health system, hospital bed reductions and increasing social and medical frailty have led to the phenomenon of "outliers" or "outlying hospital in-patients." They are often medical patients who, because of unavailability of beds in their clinically appropriate ward, are admitted wherever unoccupied beds are. The present work is aimed to systematically review literature about quality and safety of care for patients admitted to clinically inappropriate wards. METHODS: We performed a systematic review of studies investigating outliers, published in peer-reviewed journals with no time restrictions. Search and screening were conducted by two independent researchers (MLR and ER). Studies were considered potentially eligible for this systematic review if aimed to assess the quality and/or the safety of care for patients admitted to clinically inappropriate units. Our search was supplemented by a hand search of references of included studies. Given the heterogeneity of studies, results were analyzed thematically. We used PRISMA guidelines to report our findings. RESULTS: We collected 17 eligible papers and grouped them into six thematic categories. Despite their methodological limits, the included studies show increased trends in mortality and readmissions among outliers. Quality of care and patient safety are compromised as patients and health professionals declare and risk analysis displays. Reported solutions are often multicomponent, stress early discharge but have not been investigated in the control group. CONCLUSIONS: Published literature cannot definitely conclude on the quality and safety of care for patients admitted to clinically inappropriate wards. As they may represent a serious threat for quality and safety, and moreover often neglected and under valued, well-designed and powered prospective studies are urgently needed.

Population diversity of the genetically determined TTR expression in human tissues and its implications in TTR amyloidosis.

BACKGROUND: Transthyretin (TTR) amyloidosis is a hereditary disease with a complex genotype-phenotype correlation. We conducted a literature survey to define the clinical landscape of TTR amyloidosis across populations worldwide. Then, we investigated whether the genetically determined TTR expression differs among human populations, contributing to the differences observed in patients. Polygenic scores for genetically determined TTR expression in 14 clinically relevant tissues were constructed using data from the GTEx (Genotype-Tissue Expression) project and tested in the samples from the 1,000 Genomes Project. RESULTS: We observed differences among the ancestral groups and, to a lesser extent, among the investigated populations within the ancestry groups. Scandinavian populations differed in their genetically determined TTR expression of skeletal muscle tissue with respect to Southern Europeans (p = 6.79*10-6). This is in line with epidemiological data related to Swedish and Portuguese TTR Val30Met endemic areas. Familial amyloidotic cardiomyopathy (TTR deposits occur primarily in heart tissues) presents clinical variability among human populations, a finding that agrees with the among-ancestry diversity of genetically determined TTR expression in heart tissues (i.e., Atrial Appendage p = 4.55*10-28; Left Ventricle p = 6.54*10-35). CONCLUSIONS: Genetically determined TTR expression varied across human populations. This might contribute to the genotype-phenotype correlation of TTR amyloidosis.

E-learning in order to improve drug prescription for hospitalized older patients: a cluster-randomized controlled study.

AIMS: The aim of the study was to evaluate the effect of an e-learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients. METHODS: Twenty geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug-drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re-hospitalizations were other secondary outcomes assessed at the 12-month follow-up. RESULTS: A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87-1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34-1.28) and potentially severe DDI (OR 0.86 95%CI 0.63-1.15) at discharge, nor in mortality rates and incidence of re-hospitalization at 12-month follow-up. CONCLUSIONS: This e-learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population.

Explorative genetic association study of GSTT2B copy number variant in complex disease risks.

BACKGROUND: Glutathione S-transferases (GSTs) are the main phase II enzymes involved in cellular detoxification. Through phase I and phase II detoxification reactions, the cell is able to detoxify endogenous and exogenous toxic compounds. AIMS: This study focused attention on the GSTT2B copy number variant (CNV) in order to explore its involvement in the genetic pre-disposition to asthma, Alzheimer's disease (AD), allergic rhinitis (AR), essential hypertension (EH), hypothyroidism and recurrent miscarriage (RM). METHODS: The study population consists of 1225 individuals divided into six case-control groups. The genotyping of the GSTT2B CNV was performed by using a duplex-PCR. Odds Ratios (ORs) were calculated, adjusting for the confounding variables, to estimate the association between GSTT2B CNV and the disease status. RESULTS: The χ(2)-test and ORs did not show any association between this genetic marker and pathological phenotypes. CONCLUSION: The data highlights that GSTT2B CNV is not associated with the investigated complex diseases in Italian patients. However, further investigations are necessary to replicate these findings in larger sample sizes and to explore other health-related phenotypes.

GSTA1*-69C/T and GSTO2*N142D as asthma- and allergy-related risk factors in Italian adult patients.

1. Asthma and allergies are characterized by variable and subjective symptoms influenced by many genes, molecular mechanisms and environmental factors. The presence of inflammation and oxidative stress in the airways are important biochemical features of asthma and respiratory allergies. Glutathione S-transferase (GSTs) enzymes play an important role in cellular protection against inflammation, and functional genetic polymorphisms in GST genes show a significant association with asthma and allergy risk. Specifically, our previous study on asthmatic children highlighted GSTA1 and GSTO2 as novel susceptibility loci for asthma. 2. In the present study we focused our attention on GSTA1*-69C/T (rs3957357) and GSTO2*N142D (rs156697) polymorphisms to confirm our previous results in an independent adult study population and to clarify whether GSTA1 and GSTO2 gene polymorphisms are involved in a non-discriminative pathway towards asthma and respiratory allergy. 3. To accomplish this, we recruited 103 patients with respiratory allergies, 199 patients with asthma and 200 healthy controls. Genomic DNA extracted from buccal cells was screened for GSTA1*-69C/T and GSTO2*N142D single nucleotide polymorphisms. 4. The GSTA1*-69T and GSTO2*D142 variants are both associated with a significantly increased risk of asthma, whereas only GSTA1*-69C/T is significantly associated with allergies. These outcomes confirm the involvement of GSTO2 loci in asthma and suggest that GSTA1 is a common risk factor for asthma and allergies.

GSTO2*N142D gene polymorphism associated with hypothyroidism in Italian patients.

Hypothyroidism is a multifactorial endocrinal disease characterized by abnormally low thyroid hormone production. Thyroiditis is one of the primary causes of hypothyroidism, as it is an increasing level of inflammation in the thyroid gland that could be due to a failure of the anti-inflammatory response. Glutathione S-transferases are biomarkers of inflammation and oxidative stress. These phase II enzymes play a relevant role in detoxifying xenobiotic compounds. Particular attention has been focused on GSTA1, GSTM1, GSTO2, GSTP1, and GSTT1 genes to evaluate if GST gene polymorphisms are associated with hypothyroidism. We screened a case-control population (patients with hypothyroidism n = 110, controls n = 122) to analyze GST gene polymorphisms. GST SNPs were determined using the PCR-RFLP method, while GST null polymorphisms were determined using a Multiplex PCR. In this study, we found differences in genotype distribution between hypothyroid individuals and controls only for the GSTO2*N142D polymorphism. Logistic regression analysis, after adjustment for age and sex, confirmed this positive association (OR = 4.56; 95 % CI 1.22-17.00; p = 0.009). The GSTO2 enzyme can catalyze several reactions important for countering oxidative stress: subjects with the D142 allele may have a deficiency in the antioxidant enzymatic system. A decrease in antioxidant capacity may trigger increased oxidative stress. Previous studies have highlighted the role of GST enzymes in inflammation disorders, but no data are available on their role in hypothyroidism. Our results suggest that GSTO2 could increase disease risk susceptibility and could act as a risk factor for hypothyroidism in Italian patients.

Glutathione S-transferase polymorphisms, asthma susceptibility and confounding variables: a meta-analysis.

Oxidative stress is one of the main risk factors for asthma development. Glutathione S-transferases play an important role in antioxidant defences and may influence asthma susceptibility. In particular, GSTM1 and GSTT1 positive/null genotypes and the GSTP1 Ile105 Val polymorphism have been analyzed in a number of genetic association studies, with conflicting outcomes. Two previous meta-analyses have attempted to clarify the associations between GST genes and asthma, but these studies have also showed contrasting results. Our aim was to perform a meta-analysis that included independent genetic association studies on GSTM1, GSTP1, and GSTT1, evaluating also the effect of potential confounding variables (i.e. ethnicity, population age, and urbanization). Systematic review and meta-analysis of the effects of GST genes on asthma were conducted. The meta-analyses were performed using a fixed or, where appropriate, random effects model. The meta-analysis of the GSTM1 (n = 35), GSTT1 (n = 31) and GSTP1 (n = 28) studies suggests that no significant associations with asthma susceptibility were observed for GSTM1 and GSTP1 gene polymorphisms, whereas a significant outcome was detected for the GSTT1 positive/null genotype (pooled OR = 1.33, 95 %CI = 1.10-1.60). However, high between-study heterogeneity was identified in all the general analyses (p heterogenetity < 0.05). The stratification analysis seems to explain the heterogeneity only in few cases. This picture is probably due to the interactive process of genetics and environment that characterizes disease pathogenesis. Further studies on interactions of GST genes with the potential oxidative stress sources and with other antioxidant genes are needed to explain the role of GST enzymes in asthma.

Hospitalization and mortality for acute exacerbation of asthma: an Italian population-based study.

Asthma is an ever-increasing disease with a highly variable prevalence among different ethnic groups. Information on hospital admission for acute exacerbation of asthma in adult patients and data regarding short-term prognosis of these patients are limited. We, thus, performed an epidemiological study on hospital admission for asthma acute exacerbation in Italy using hospital discharge database records derived from all Italian hospitals. Patients > 15 years old were identified using clinical Modification (ICD-9-CM) codes. Information on baseline characteristics, vital status at discharge, duration of hospitalization, and up to five secondary discharge diagnoses was collected. Comorbidity was evaluated using the Charlson comorbidity index (CCI). During the observation period (2013-2014), 20,056 patients with asthma acute exacerbation were hospitalized. Median length of hospitalization was 7.9 days (interquartile range 4-10) and mean in-hospital mortality was 0.8%. In-hospital mortality and length of hospitalization varied among different regions (from 0 to 2.9% and from 6.5 to 8.9 days, respectively). Old age, invasive and non-invasive mechanical ventilation, and CCI resulted as significantly associated with higher in-hospital mortality. Our study results, on a large sample of patients, confirm that hospitalization for asthma acute exacerbation is not uncommon among Italian current population. Older age, high CCI, and use of ventilator support were associated with a higher mortality rate. These findings should be analyzed to set up appropriate health care policies on patients with asthma.

Clinical nutrition in internal medicine: An Italian survey by the scientific societies FADOI and SINPE.

OBJECTIVES: Patients hospitalized in internal medicine are frequently malnourished or at risk for malnutrition. The aim of this study, conducted by the Federation of Associations of Hospital Internists (FADOI) and the Italian Society of Artificial Nutrition and Metabolism (SINPE) was to assess the nutritional management of internal medicine inpatients in Italy, to identify critical issues and formulate practical proposals to improve nutritional treatment. METHODS: From February to April 2021, FADOI and SINPE conducted a national web-based survey, including a 13 multiple-choice item questionnaire related to three key areas: screening and assessment of malnutrition and associated/overlapping sarcopenia and dysphagia; specialist consultations; and management of nutritional support. RESULTS: Responding to the questionnaire were 266 physicians among FADOI members (10.76%). Screening for malnutrition is performed with validated tests, within standardized care pathways, or routinely, only by 22% of participants. Global Leadership Initiative on Malnutrition criteria for diagnosis of malnutrition are little used (20%). Screening for sarcopenia was insufficient as the systematic use of assessment tools (handgrip/chair test) was minimal (3%). Screening for dysphagia is not a routine procedure for at-risk patients according to 33% of participants. Systematic involvement of clinical nutrition services/units in the management of malnourished/sarcopenic patients was reported by only 17% of internists. CONCLUSIONS: To overcome the critical issues that emerged from the present study, FADOI and SINPE experts proposed practical solutions to promote the application of the most recent guidelines and to improve awareness and sensitivity to nutritional management in internal medicine real-life settings.

Intentional Rounding versus Standard of Care for Patients Hospitalised in Internal Medicine Wards: Results from a Cluster-Randomised Nation-Based Study.

The aim of the study was to explore the effects of Intentional Rounding, a regular-based proactive patient monitoring, on falls and pressure ulcers in internal medicine units. This is a cluster-randomised controlled study, where units were assigned (1:1) to Intentional Rounding (intervention group) or Standard of Care (control group). The primary outcome was the cumulative incidence of falls and new pressure ulcers. These events were considered separately as secondary endpoints, together with the number of bell calls and the evaluation of patient satisfaction. Primary analyses were carried out on the modified intention-to-treat population (hospitalisation of at least 10 days). Recruitment occurred between October 2019 and March 2020, at which time the study was prematurely closed due to the COVID-19 pandemic. Enrolment totalled 1822 patients at 26 sites; 779 patients were included in the modified intention-to-treat analysis. The intervention group had a lower risk of falls (adjusted incidence rate ratio 0.14; 95% confidence interval, 0.02-0.78; p = 0.03). There were no statistical differences in new pressure ulcers or the cumulative incidence of both adverse events. Mean bell calls for each patient were 15.4 ± 24.1 in the intervention group and 13.7 ± 20.5 in the control group (p = 0.38). Additionally, patient satisfaction in the intervention group was almost at the maximum level. Our study supports the usefulness of Intentional Rounding in a complex and vulnerable population such as that hospitalised in internal medicine units.

Glutathione S-transferase variants as risk factor for essential hypertension in Italian patients.

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.

Functional polymorphisms of GSTA1 and GSTO2 genes associated with asthma in Italian children.

BACKGROUND: Asthma is an airway disorder characterized by bronchial inflammation. An imbalance between the oxidative forces and the antioxidant defense systems has been implicated in the pathogenesis of asthma. Glutathione S-transferases (GSTs) play an important role in cellular protection against inflammation. Several studies have investigated the genetic variability of GSTM1, GSTP1 and GSTT1 enzymes in asthma development with conflicting results. Moreover, in our previous independent case-control study on GSTs and asthma, we have found that GSTA1 and GSTO2 gene polymorphisms are associated with asthma. The aim of the present study is to analyze if some functional polymorphisms of GSTA1, GSTM1, GSTP1, GSTO2 and GSTT1 are associated with asthma in pediatric patients from Chieti (Italy). METHODS: In this study, we performed an association study on 127 asthmatic children and 126 controls. We screened single nucleotide polymorphisms at GSTA1, GSTO2 and GSTP1 loci. The effects of GSTM1 and GSTT1 null genotype were also investigated. RESULTS: The GSTA1*-69T and GSTO2*D142 variants are associated with the significant increased risk of asthma development in our study population, while GSTM1, GSTP1 and GSTT1 genotype distributions were nearly equal between the control group and asthmatics. CONCLUSIONS: Confirming our previous study, these findings suggest that the GSTA1 and the GSTO2 are asthma susceptible genes involved in increasing the risk of asthma development in the Italian population.