The association of genetic factors with serum calretinin levels in asbestos-related diseases.

BACKGROUND: Asbestos exposure is associated with different asbestos-related diseases, including malignant mesothelioma (MM). MM diagnosis is confirmed with immunohistochemical analysis of several markers, including calretinin. Increased circulating calretinin was also observed in MM. The aim of the study was to determine if CALB2 polymorphisms or polymorphisms in genes that can regulate calretinin expression are associated with serum calretinin levels or MM susceptibility. SUBJECTS AND METHODS: The study included 288 MM patients and 616 occupationally asbestos-exposed subjects without MM (153 with asbestosis, 380 with pleural plaques and 83 without asbestos-related disease). Subjects were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1 and SEPTIN7 genes using competitive allele-specific polymerase chain reaction (PCR). Serum calretinin was determined with ELISA in 545 subjects. Nonparametric tests, logistic regression and receiver operating characteristic (ROC) curve analysis were used for statistical analysis. RESULTS: Carriers of at least one polymorphic CALB2 rs889704 allele had lower calretinin levels (P = 0.036). Carriers of two polymorphic MIR335 rs3807348 alleles had higher calretinin (P = 0.027), while carriers of at least one polymorphic NRF1 rs13241028 allele had lower calretinin levels (P = 0.034) in subjects without MM. Carriers of two polymorphic E2F2 rs2075995 alleles were less likely to develop MM (odds ratio [OR] = 0.64, 95% confidence interval [CI] = 0.43-0.96, P = 0.032), but the association was no longer significant after adjustment for age (P = 0.093). Optimal serum calretinin cut-off values differentiating MM patients from other subjects differed according to CALB2, NRF1, E2F2, and MIR335 genotypes. CONCLUSIONS: The results of presented study suggest that genetic variability could influence serum calretinin levels. These findings could contribute to a better understanding of calretinin regulation and potentially to earlier MM diagnosis.

Serum Calretinin and Genetic Variability as a Prognostic and Predictive Factor in Malignant Mesothelioma.

Calretinin is a promising diagnostic biomarker for malignant mesothelioma (MM), but less is known about its prognostic role. Our aim was to evaluate the association between serum calretinin concentration or genetic factors and the survival or outcome of cisplatin-based chemotherapy in MM. Our study included 265 MM patients. Serum calretinin concentration was determined using ELISA. Patients were genotyped for seven polymorphisms in CALB2, E2F2, MIR335, NRF1, and SEPTIN7 using competitive allele-specific PCR. Nonparametric tests, logistic regression, and survival analysis were used for statistical analysis. Higher serum calretinin concentration was associated with shorter progression-free (PFS) (HR = 1.18 (1.02-1.37), p = 0.023) and overall survival (OS) (HR = 1.20 (1.03-1.41), p = 0.023), but the association was not significant after adjusting for clinical factors (HR = 1.05 (0.85-1.31), p = 0.653 and HR = 1.06 (0.84-1.34), p = 0.613, respectively). SEPTIN7 rs3801339 and MIR335 rs3807348 were associated with survival even after adjustment (HR = 1.76 (1.17-2.64), p = 0.007 and HR = 0.65 (0.45-0.95), p = 0.028, respectively). Calretinin concentration was higher in patients who progressed after treatment with cisplatin-based chemotherapy (1.68 vs. 0.45 ng/mL, p = 0.001). Calretinin concentration above 0.89 ng/mL was associated with shorter PFS and OS from the start of chemotherapy (HR = 1.88 (1.28-2.77), p = 0.001 and HR = 1.91 (1.22-2.97), p = 0.004, respectively), even after adjusting for clinical factors (p < 0.05). MIR335 rs3807348 was associated with a better response to chemotherapy (OR = 2.69 (1.17-6.18), p = 0.020). We showed that serum calretinin is associated with survival and chemotherapy treatment outcomes in MM and could serve as a predictive biomarker.

Serum Calretinin as a Biomarker in Malignant Mesothelioma.

The early diagnosis of malignant mesothelioma (MM) could improve the prognosis of MM patients. To confirm an MM diagnosis, an immunohistochemical analysis of several tumor tissue markers, including calretinin, is currently required. Our aim is to evaluate serum calretinin as a potential biomarker in asbestos-related diseases, especially in MM. Our study includes 549 subjects: 164 MM patients, 117 subjects with asbestosis, 195 subjects with pleural plaques and 73 occupationally asbestos-exposed subjects without asbestos-related diseases. The serum calretinin concentration was determined with a commercially available enzyme immunoassay. Data on the soluble mesothelin-related peptides (SMRP) concentration are available from previous studies. MM patients had a significantly higher calretinin concentration than subjects without disease, subjects with pleural plaques or subjects with asbestosis (all p < 0.001). The histological type was significantly associated with serum calretinin: patients with sarcomatoid MM had lower calretinin than patients with the epithelioid type (p = 0.001). In a ROC curve analysis, the area under the curve for calretinin concentration predicting MM was 0.826 (95% CI = 0.782-0.869; p < 0.001). At the cutoff value of 0.32 ng/mL, sensitivity was 0.683, while specificity was 0.886. The combination of calretinin and SMRP had the highest predictive value. Calretinin is a useful biomarker that can distinguish MM from other asbestos-related diseases and could, therefore, contribute to an earlier non-invasive diagnosis of MM.

Impact of attention deficit hyperactivity disorder on metabolic control in adolescents with type1 diabetes.

OBJECTIVE: Diabetes mellitus type 1 (T1D) incidence is increasing in pediatric population. Good metabolic control, measured by glycated hemoglobin (HbA1c), significantly reduces the risk for chronic complications. Comorbid disorders, including attention-deficit hyperactivity disorder (ADHD), may influence glycemic control. To date little is known about the prevalence of ADHD among adolescents with T1D and its influence on diabetes self-management. Therefore, we aimed to identify adolescents with T1D and ADHD and assess the effect of ADHD on metabolic control. METHOD: This cross-sectional case-control study included 101 patients (11-17 years old) with T1D. Development and Well-Being Assessment (DAWBA) questionnaire and subsequent psychiatric clinical examination were used to identify ADHD in a group with T1D. Indicators of metabolic control were collected from available medical documentation for preceding 12 months and compared between the group of patients with T1D and ADHD and the group of T1D patients without ADHD. RESULTS: ADHD was diagnosed in 11.9% adolescents with T1D (12 of 101). We found a statistically significant difference (p = .022) in HbA1c between the two groups - higher in the group with T1D and ADHD (8.4% or 68.3 mmol/mol) than in the group with T1D without ADHD (7.8% or 61.7 mmol/mol). CONCLUSIONS: Almost 12% of adolescents with type 1 diabetes were diagnosed with ADHD and they had poorer glycemic control. Adolescents with T1D and ADHD must be diagnosed early and offered appropriate treatment focused on preventing negative ADHD impact on metabolic control.

Angiotensin-converting enzyme inhibitors as a cause of isolated angioedema in a Slovenian population.

INTRODUCTION: Angioedema (AE) is a localized swelling of the subcutaneous tissue and mucosa. We aimed to identify how often AE is associated with angiotensin-converting enzyme inhibitor (ACEI-AE) therapy and whether the severity of AE episodes in these patients differs from the severity in idiopathic AE (IAE). METHODS: We included patients with AE that were referred to a tertiary allergy clinic from 2005 to 2014. We obtained data on AE location, severity, number, and treatment of episodes from patient medical files. Patients treated with ACEI were contacted to obtain follow-up data on the effect of ACEI discontinuation. RESULTS: A total of 603 patients with AE were referred (59.9% women) to our clinic. A total of 36.9% had AE associated with urticaria or anaphylaxis. Among 381 patients with isolated AE, 10.5% of the patients were diagnosed with identified causes. The proportion of ACEI-AE was 27.1% to 37.9% (95% CI); others were classified as IAE. ACEI-AE cases had more severe episodes compared to IAE cases, which were more likely to be treated by a family doctor or even hospitalized. CONCLUSION: ACEI was shown to be the most frequent removable cause of isolated AE. About two-thirds of AE cases taking ACEI were resolved after removal of the drug.