Previous reports relating coronary artery disease and functional variants of the renin-angiotensin system have been contradictory in establishing the role of these polymorphisms in coronary artery ...disease (CAD) development. The aim of the present study is to determine if there is an association between the M235T variant of the angiotensinogen gene and severity of coronary artery disease in patients with clinically suspected disease undergoing cineangiogram.
The angiotensinogen M235T variant was analyzed in 871 consecutive patients with clinically suspected coronary artery disease submitted to coronary angiography study. Three different angiographic scores were used to determine severity of the disease analyzing 20 coronary segments. All patients were evaluated considering classical risk factors for coronary artery disease throughout a medical oriented questionnaire, anthropometric measures, and blood glucose and lipid profile determination.
Presence of the 235T allele was associated with higher angiographic extension scores in univariate analysis (
p
<
0.05). The 235T allele was also associated with an increased risk of presenting 3-vessel disease (
p
<
0.05). In addition, the T allele was significantly associated with higher Gensini's scores both in univariate (
p
=
0.05) and multivariate analyses (
p
<
0.05). Finally, a 1.86 fold increase in the risk of multivessel disease (95% CI: 1.174–2.947) was associated with the TT genotype independently of other cardiovascular risk factors associated with disease extension.
The data hereby provide further support for the association between angiotensinogen M235T polymorphism and CAD severity independently of other cardiovascular risk factors.
Clustering of cardiovascular risk factors is observed in metabolic syndrome (MS), but the relative contribution of different factors to determine outcomes remains largely unknown. We investigated the ...influence of gender in the effect of MS in coronary vascular lesions in 385 patients who underwent first time coronary artery disease (CAD) assessment through coronary angiography.
Patients were stratified in two groups: metabolic syndrome (MS,
N
=
190) and non-metabolic syndrome (NMS,
N
=
195), according to standard criteria. Two vascular scores related to extension and severity of vascular lesions were determined by systematic analysis of 20 coronary segments.
MS was more prevalent in females (58.7 vs. 39.7%,
p
=
0.0005) and hypertension and low-HDL were the leading prevalent factors in the MS group. Scores for extension and severity of lesions were higher in the MS than in the NMS group (2.10
±
1.75 vs. 1.75
±
1.58;
p
=
0.01, and 1.49
±
1.29 vs. 1.25
±
1.15;
p
=
0.03, respectively). The impact of MS in CAD scores was more pronounced in females (OR 2.2, 95% CI 1.1–4.3,
p
=
0.02) than in males (OR 1.5, 95% CI 0.8–2.7,
p
=
0.17). Non-HDL cholesterol was the only risk factor influencing the scores in a gender specific manner, showing an increased impact in the female gender. Normal coronary angiograms were more frequent in females (
p
=
0.0001), especially in NMS. Collectively, these data suggest that MS is related to higher extension and severity of vascular lesions in this population regardless of gender but lipids and anthropometric parameters may differentially modulate the MS effect in a particular gender.
Although applied over extremely short timescales, artificial selection has dramatically altered the form, physiology, and life history of cultivated plants. We have used RNAseq to define both gene ...sequence and expression divergence between cultivated tomato and five related wild species. Based on sequence differences, we detect footprints of positive selection in over 50 genes. We also document thousands of shifts in gene-expression level, many of which resulted from changes in selection pressure. These rapidly evolving genes are commonly associated with environmental response and stress tolerance. The importance of environmental inputs during evolution of gene expression is further highlighted by large-scale alteration of the light response coexpression network between wild and cultivated accessions. Human manipulation of the genome has heavily impacted the tomato transcriptome through directed admixture and by indirectly favoring nonsynonymous over synonymous substitutions. Taken together, our results shed light on the pervasive effects artificial and natural selection have had on the transcriptomes of tomato and its wild relatives.
We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs ...were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development.
Epidemiological studies reveal a link between osteoporosis and the risk of ischemic cardiovascular disease. We illustrate an association between coronary calcification and bone microarchitecture in ...older adults based on the SPAH study. This cross-sectional research comprised 256 individuals subjected to cardiac coronary computed tomography angiography (CCTA) for coronary artery calcification (CAC), high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia and radius with standardized z score parameters, and dual-energy X-ray absorptiometry (DXA) to evaluate bone status. We used Student's t test and the Mann-Whitney and Chi-squared tests for comparison of basal measurements. Association analysis was performed using the Poisson regression model with adjustment for CAC and sex. Multivariate analysis revealed different bone variables for predicting CAC in DXA and HR-pQCT scenarios. Although most of the bone parameters are related to vascular calcification, only cortical porosity (Ct.Po) remained uniform by HR-pQCT. Results for were as follows: the tibia-women (exp β = 1.12 (95% CI 1.10-1.13, p < 0.001) and men (exp β = 1.44, 95% CI 1.42-1.46, p < 0.001); the radius-women (exp β = 1.07 (95% CI 1.07-1.08, p < 0.001) and men (exp β = 1.33 (95% CI 1.30-1.37, p < 0.001). These findings suggest an inverse relationship between CAC and cortical bone content, as assessed by HR-pQCT, with higher coronary calcification in individuals older than 65 years.
A polymorphism of glycoprotein IIb/IIIa has been associated with myocardial infarction and restenosis after percutaneous coronary intervention. The influence on outcome and the interaction of the ...Pl(A1) genotype with classic risk factors for coronary artery disease (CAD) were characterized in patients with chronic CAD followed prospectively for 3 years. Pl(A1) genotypes were assessed in 592 patients enrolled in the Medical, Angioplasty, or Surgery Study II, a randomized trial comparing treatments for patients with CAD and preserved left ventricular function. The incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization were determined in each genotype group. Risk was assessed with the Cox proportional-hazards model. The clinical characteristics and treatment of each genotype were similar. Although the composite end point tended to be more common in patients with the Pl(A2) allele, only smokers with the Pl(A2) allele had a significantly increased incidence of the composite end point (p = 0.01). Moreover, a 2.2-fold increased risk was apparent in smokers with the Pl(A2) allele (p = 0.03). Thus, taken together, these data provide support for the interaction effect between smoking and the Pl(A1) gene variant. Smokers with the Pl(A2) polymorphism of platelet glycoprotein IIIa are at greater risk for subsequent cardiac events in stable coronary disease.
A polymorphism of glycoprotein IIb/IIIa has been associated with myocardial infarction and restenosis after percutaneous coronary intervention. The influence on outcome and the interaction of the Pl
...A1 genotype with classic risk factors for coronary artery disease (CAD) were characterized in patients with chronic CAD followed prospectively for 3 years. Pl
A1 genotypes were assessed in 592 patients enrolled in the Medical, Angioplasty, or Surgery Study II, a randomized trial comparing treatments for patients with CAD and preserved left ventricular function. The incidence of the composite end point of cardiac death, myocardial infarction, and refractory angina requiring revascularization were determined in each genotype group. Risk was assessed with the Cox proportional-hazards model. The clinical characteristics and treatment of each genotype were similar. Although the composite end point tended to be more common in patients with the Pl
A2 allele, only smokers with the Pl
A2 allele had a significantly increased incidence of the composite end point (p = 0.01). Moreover, a 2.2-fold increased risk was apparent in smokers with the Pl
A2 allele (p = 0.03). Thus, taken together, these data provide support for the interaction effect between smoking and the Pl
A1 gene variant. Smokers with the Pl
A2 polymorphism of platelet glycoprotein IIIa are at greater risk for subsequent cardiac events in stable coronary disease.
Solanum pennellii is a wild tomato species endemic to Andean regions in South America, where it has evolved to thrive in arid habitats. Because of its extreme stress tolerance and unusual morphology, ...it is an important donor of germplasm for the cultivated tomato Solanum lycopersicum. Introgression lines (ILs) in which large genomic regions of S. lycopersicum are replaced with the corresponding segments from S. pennellii can show remarkably superior agronomic performance. Here we describe a high-quality genome assembly of the parents of the IL population. By anchoring the S. pennellii genome to the genetic map, we define candidate genes for stress tolerance and provide evidence that transposable elements had a role in the evolution of these traits. Our work paves a path toward further tomato improvement and for deciphering the mechanisms underlying the myriad other agronomic traits that can be improved with S. pennellii germplasm.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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