No evidence for an association between the -36A>C phospholamban gene polymorphism and a worse prognosis in heart failure

Background: In Brazil, heart failure leads to approximately 25,000 deaths per year. Abnormal calcium handling is a hallmark of heart failure and changes in genes encoding for proteins involved in the re-uptake of calcium might harbor mutations leading to inherited cardiomyopathies. Phospholamban (PLN) plays a prime role in cardiac contractility and relaxation and mutations in the gene encoding PLN have been associated with dilated cardiomyopathy. In this study, our objective was to determine the presence of the -36A>C alteration in PLN gene in a Brazilian population of individuals with HF and to test whether this alteration is associated with heart failure or with a worse prognosis of patients with HF. Methods: We genotyped a cohort of 881 patients with HF and 1259 individuals from a cohort of individuals from the general population for the alteration -36A>C in the PLN gene. Allele and genotype frequencies were compared between groups (patients and control). In addition, frequencies or mean values of different phenotypes associated with cardiovascular disease were compared between genotypic groups. Finally, patients were prospectively followed-up for death incidence and genotypes for the -36A>C were compared regarding mortality incidence in HF patients. Results: No significant association was found between the study polymorphism and HF in our population. In addition, no association between PLN -36A>C polymorphism and demographic, clinical and functional characteristics and mortality incidence in this sample of HF patients was observed. Conclusion: Our data do not support a role for the PLN -36A>C alteration in modulating the heart failure phenotype, including its clinical course, in humans

The Farsi version of the Hypomania Check-List 32 (HCL-32): Applicability and indication of a four-factorial solution

Background: Data from the Iranian population for hypomania core symptom clusters are lacking. The aim of the present study was therefore to apply the Farsi version of the Hypomania-Check-List 32 (HCL-32), and to explore its factorial structure.Methods: A total of 163 Iranian out-patients took part in the study; 61 suffered from Major Depressive Disorder (MDD), and 102 suffered from Bipolar Disorders (BP). Participants completed the Mood Disorder Questionnaire (MDQ) and the Hypomania Checklist (HCL-32). Exploratory factor analyses were used to examine the properties of the HCL-32. A ROC-curve analysis was performed to calculate sensitivity and specificity.Results: The HCL-32 differentiated between patients with MDD and with BP. Psychometric properties were satisfactory: sensitivity: 73; specificity: 91. MDQ and HCL-32 did correlate highly. No differences were found between patients suffering from BP I and BP II.Discussion: Instead of the two-factorial structure of the HCL-32 reported previously, the present pattern of factorial results suggest a distinction between four factors: two broadly positive dimensions of hypomania ("physically and mentally active"; "positive social interactions") and two rather negative dimensions ("risky behavior and substance use"; "difficulties in social interaction and impatience").Conclusion: The Farsi version of the HCL-32 proved to be applicable, and therefore easy to introduce within a clinical context. The pattern of results suggests a four factorial solution. © 2011 Haghighi et al; licensee BioMed Central Ltd

Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices

Emerging evidence suggests that DNA methylation plays an expansive role in the central nervous system (CNS). Large-scale whole genome DNA methylation profiling of the normal human brain offers tremendous potential in understanding the role of DNA methylation in brain development and function.Using methylation-sensitive SNP chip analysis (MSNP), we performed whole genome DNA methylation profiling of the prefrontal, occipital, and temporal regions of cerebral cortex, as well as cerebellum. These data provide an unbiased representation of CpG sites comprising 377,509 CpG dinucleotides within both the genic and intergenic euchromatic region of the genome. Our large-scale genome DNA methylation profiling reveals that the prefrontal, occipital, and temporal regions of the cerebral cortex compared to cerebellum have markedly different DNA methylation signatures, with the cerebral cortex being hypermethylated and cerebellum being hypomethylated. Such differences were observed in distinct genomic regions, including genes involved in CNS function. The MSNP data were validated for a subset of these genes, by performing bisulfite cloning and sequencing and confirming that prefrontal, occipital, and temporal cortices are significantly more methylated as compared to the cerebellum.These findings are consistent with known developmental differences in nucleosome repeat lengths in cerebral and cerebellar cortices, with cerebrum exhibiting shorter repeat lengths than cerebellum. Our observed differences in DNA methylation profiles in these regions underscores the potential role of DNA methylation in chromatin structure and organization in CNS, reflecting functional specialization within cortical regions

Left ventricular remodeling in swine after myocardial infarction: a transcriptional genomics approach

Despite the apparent appropriateness of left ventricular (LV) remodeling following myocardial infarction (MI), it poses an independent risk factor for development of heart failure. There is a paucity of studies into the molecular mechanisms of LV remodeling in large animal species. We took an unbiased molecular approach to identify candidate transcription factors (TFs) mediating the genetic reprogramming involved in post-MI LV remodeling in swine. Left ventricular tissue was collected from remote, non-infarcted myocardium, 3 weeks after MI-induction or sham-surgery. Microarray analysis identified 285 upregulated and 278 downregulated genes (FDR < 0.05). Of these differentially expressed genes, the promoter regions of the human homologs were searched for common TF binding sites (TFBS). Eighteen TFBS were overrepresented >two-fold (p < 0.01) in upregulated and 13 in downregulated genes. Left ventricular nuclear protein extracts were assayed for DNA-binding activity by protein/DNA array. Out of 345 DNA probes, 30 showed signal intensity changes >two-fold. Five TFs were identified in both TFBS and protein/DNA array analyses, which showed matching changes for COUP-TFII and glucocorticoid receptor (GR) only. Treatment of swine with the GR antagonist mifepristone after MI reduced the post-MI increase in LV mass, but LV dilation remained unaffected. Thus, using an unbiased approach to study post-MI LV remodeling in a physiologically relevant large animal model, we identified COUP-TFII and GR as potential key mediators of post-MI remodeling

Genetic Association Study Identifies HSPB7 as a Risk Gene for Idiopathic Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a structural heart disease with strong genetic background. Monogenic forms of DCM are observed in families with mutations located mostly in genes encoding structural and sarcomeric proteins. However, strong evidence suggests that genetic factors also affect the susceptibility to idiopathic DCM. To identify risk alleles for non-familial forms of DCM, we carried out a case-control association study, genotyping 664 DCM cases and 1,874 population-based healthy controls from Germany using a 50K human cardiovascular disease bead chip covering more than 2,000 genes pre-selected for cardiovascular relevance. After quality control, 30,920 single nucleotide polymorphisms (SNP) were tested for association with the disease by logistic regression adjusted for gender, and results were genomic-control corrected. The analysis revealed a significant association between a SNP in HSPB7 gene (rs1739843, minor allele frequency 39%) and idiopathic DCM (p = 1.06×10−6, OR = 0.67 [95% CI 0.57–0.79] for the minor allele T). Three more SNPs showed p < 2.21×10−5. De novo genotyping of these four SNPs was done in three independent case-control studies of idiopathic DCM. Association between SNP rs1739843 and DCM was significant in all replication samples: Germany (n = 564, n = 981 controls, p = 2.07×10−3, OR = 0.79 [95% CI 0.67–0.92]), France 1 (n = 433 cases, n = 395 controls, p = 3.73×10−3, OR = 0.74 [95% CI 0.60–0.91]), and France 2 (n = 249 cases, n = 380 controls, p = 2.26×10−4, OR = 0.63 [95% CI 0.50–0.81]). The combined analysis of all four studies including a total of n = 1,910 cases and n = 3,630 controls showed highly significant evidence for association between rs1739843 and idiopathic DCM (p = 5.28×10−13, OR = 0.72 [95% CI 0.65–0.78]). None of the other three SNPs showed significant results in the replication stage

Neuropsychological function is related to irritable bowel syndrome in women with premenstrual syndrome and dysmenorrhea

Background There is increasing evidence demonstrating the co-occurrence of primary dysmenorrhea (PD), premenstrual syndrome (PMS), and irritable bowel syndrome (IBS) in women. This study aimed to investigate whether women who have symptoms of IBS in addition to PD and PMS also report more severe or frequent menstruation-associated symptoms and psychological complications compared to women with PD and PMS alone. Methods The study group included 182 female University students aged 18–25 years. IBS was diagnosed using the Rome III criteria. The severity of PMS and PD was determined using a 10-point visual analog scale and PSST (Premenstrual Syndrome Screening Tool), respectively. Neuropsychological functions including cognitive function, depression score, anxiety score, stress, insomnia, daytime sleepiness, quality of life and personality were assessed using standard questionnaires. Results Of the 182 young females, 31 (17.0%) had IBS. Average days of bleeding during the menstrual cycle and mean pain severity on the PSST scale were significantly greater in the group with IBS compared to the non-IBS group (p < 0.01). The non-IBS individuals scored more favorably than the women with IBS with respect to severity of depression, insomnia, daytime sleepiness (p < 0.05). The PSST scores were significantly correlated with scores for depression (r = 0.29; p < 0.001), anxiety (r = 0.28; p < 0.001), stress (r = 0.32; p < 0.001), insomnia (r = 0.34; p < 0.001) and daytime sleepiness (r = 0.31; p < 0.001); while, they were negatively correlated with cognitive abilities (r = − 0.20; p = 0.006) and quality of life (r = − 0.42; p < 0.001). Linear regression analysis showed that the PSST scores were possibly significant factors in determining the scores for depression, anxiety, stress, quality of life, insomnia and daytime sleepiness (p < 0.05). Conclusion IBS is related to psychological comorbidities, in particular depression, sleep problems and menstrual-associated disorders. IBS may exacerbate the features of PMS which should be taken into account in the management of PMS