BACKGROUND
Genetic analysis has been successful in identifying causative mutations for individual cardiovascular risk factors. Success has been more limited in mapping susceptibility genes for clusters of cardiovascular risk traits, such as those in the metabolic syndrome.
METHODS
We identified three large families with coinheritance of early-onset coronary artery disease, central obesity, hypertension, and diabetes. We used linkage analysis and whole-exome sequencing to identify the disease-causing gene.
RESULTS
A founder mutation was identified in DYRK1B, substituting cysteine for arginine at position 102 in the highly conserved kinase-like domain. The mutation precisely cosegregated with the clinical syndrome in all the affected family members and was absent in unaffected family members and unrelated controls. Functional characterization of the disease gene revealed that nonmutant protein encoded by DYRK1B inhibits the SHH (sonic hedgehog) and Wnt signaling pathways and consequently enhances adipogenesis. Furthermore, DYRK1B promoted the expression of the key gluconeogenic enzyme glucose-6-phosphatase. The R102C allele showed gain-offunction activities by potentiating these effects. A second mutation, substituting proline for histidine 90, was found to cosegregate with a similar clinical syndrome in an ethnically distinct family.
CONCLUSIONS
These findings indicate a role for DYRK1B in adipogenesis and glucose homeostasis and associate its altered function with an inherited form of the metabolic syndrome. (Funded by the National Institutes of Health.)
ALP poisoning is a common toxicity in Iran causing high morality. This is a serious health problem in agricultural region where ALP is readily available. Withdrawal of ALP tablet from the market and introduction of safer products as rodenticides and insecticides is recommended.
Objective: The aim of this study was to determine the levels of serum pro-brain natriuretic peptide (pro-BNP) and interleukin (IL)-6 in patients with stable chronic obstructive pulmonary disease (COPD) and to correlate these markers with health-related quality of life using the COPD assessment test (CAT). Materials and Methods: Serum pro-BNP and IL-6 levels were measured in 82 patients with stable COPD. Serum pro-BNP and serum IL-6 levels, pulmonary function, and oxygen saturation (SpO2) were measured according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and CAT score. Also, the associations of both pro-BNP and IL-6 with the clinical parameters of patients were tested. Results: The serum levels of IL-6 (7.57 [5-11.16] pg/mL) and pro-BNP (120.55 [92.89-144.20] pg/mL) were higher with enhancing disease severity based on the GOLD classification (p = 0.034 and 0.068, respectively). Also, serum levels of pro-BNP (120.55 [89.50-147.90] pg/mL) and IL-6 (6.68 [4.40-11.97] pg/mL) were increased in patients with high CAT scores (p = 0.004 and 0.017, respectively). There was a significant positive correlation between plasma pro-BNP and IL-6 levels (r = 0.332, p = 0.002). Conclusion: The results demonstrated that with increased severity of obstruction based on the GOLD criteria both IL-6 and pro-BNP were elevated. This increase in inflammatory markers was associated with a reduced quality of life and the severity of hypoxia. These findings indicated that lowering IL-6 and pro-BNP could be useful in the management of COPD patients.
This study is the first report on HCV genotypes among Iranian subjects with different exposure categories resided in Mazandaran, where genotype 3a was found to be the most frequent genotype in thalassemia, hemophilia, and hemodialysis patients but not in IDAs. Since the addiction age is decreasing in Iran and a lot of addicts are IDAs, it might change the subtype pattern of HCV in general population.
The present study has investigated the effectiveness of staged-preconditioning, in both remote and target organs. After IP the myocardial release of the biochemical markers including, creatine phosphokinase (CPK), cardiac creatine kinase (CK-MB), cardiac troponin T (cTnT) and lactate dehydrogenase (LDH) were evaluated in patients who underwent CABG, with and without staged-preconditioning. Sixty-one patients entered the study; there were 32 patients in the staged-preconditioning group and 29 patients in the control group. All patients underwent on-pump CABG using cardiopulmonary bypass (CPB) techniques. In the staged-preconditioning group, patients underwent two stages of IP on remote (upper limb) and target organs. Each stage of preconditioning was carried out by 3 cycles of ischemia and then reperfusion. Serum levels of biochemical markers were immediately measured postoperatively at 24, 48 and 72 h. Serum CK-MB, CPK and LDH levels were significantly lower in the staged-preconditioning group than in the control group. The CK-MB release in the staged-preconditioning patients reduced by 51% in comparison with controls over 72 h after CABG. These results suggest that myocardial injury was attenuated by the effect of three rounds of both remote and target organ IP.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.