Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure

We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 × 10 -70), rs198358 (P = 8 × 10 -30) and rs632793 (P = 2 × 10 -10), and of plasma B-type natriuretic peptide with rs5068 (P = 3 × 10 -12), rs198358 (P = 1 × 10 -25) and rs632793 (P = 2 × 10 -68). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 × 10 -6 and 6 × 10 -5, respectively) and diastolic blood pressure (P = 1 × 10 -6 and 5 × 10 -5), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 × 10 -5; OR = 0.90, 95% CI = 0.85-0.95, P = 2 × 10 -4, respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.

Association of functional haem oxygenase-1 gene promoter polymorphism with polycystic kidney disease and IgA nephropathy

Background: Haem oxygenase-1 (HO-1) is a cytoprotective molecule that is reported to have a protective role in a variety of experimental models of renal injury. A functional dinucleotide repeat (GT)n polymorphism, within the HO-1 promoter, regulates HO-1 gene expression; a short number of repeats (S-allele <25) increases transcription. We report the first assessment of the role of this HO-1 gene promoter polymorphism in chronic kidney disease due to autosomal dominant polycystic kidney disease (ADPKD) and IgA nephropathy (IgAN).

Methods: The DNA from 160 patients (99% Caucasian) on renal replacement therapy (RRT) was genotyped. The primary renal disease was ADPKD in 100 patients and biopsy-proven IgAN in 60 patients.

Results: Overall, the mean age at commencement of RRT was not significantly different between patients with and without an S-allele (44.1 years versus 45.0 years, P = 0.64). In patients with ADPKD, the age at commencement of RRT was comparable regardless of the HO-1 genotype (47.7 years versus 46.7 years, P = 0.59). The same was true in patients with IgAN (38.3 years versus 42.2 years, P = 0.28).

Conclusion: This suggests that the functional HO-1 promoter polymorphism does not influence renal survival in CKD due to ADPKD or IgAN.

The Association Between Alcohol and Reflux Esophagitis, Barrett's Esophagus, and Esophageal Adenocarcinoma

Background & Aims: Alcohol consumption may increase gastroesophageal reflux symptoms, cause damage to the esophageal mucosa, and/or promote carcinogenesis. However, reports about the association between alcohol and reflux esophagitis, Barrett's esophagus, and esophageal adenocarcinoma are conflicting. Methods: Information relating to alcohol consumption, at age 21 and 5 years before the interview date, was collected from 230 reflux esophagitis, 224 Barrett's esophagus, and 227 esophageal adenocarcinoma patients and 260 frequency-matched population controls. Logistic regression analyses were used to compare alcohol consumption in the 3 case groups to controls with adjustment for potential confounders. Results: Population controls reporting gastroesophageal reflux symptoms were less likely than controls without symptoms to drink alcohol 5 years before the interview date (odds ratio [OR], 0.44, 0.20-0.99). No associations were observed between total alcohol consumption 5 years before the interview date and reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma (OR, 1.26, 0.78-2.05; OR, 0.72, 0.43-1.21; and OR, 0.75, 0.46-1.22, respectively). Wine was inversely associated with reflux esophagitis (OR, 0.45, 0.27-0.75). Total alcohol consumption at age 21 years was significantly associated with reflux esophagitis (OR, 2.24, 1.35-3.74) but not with Barrett's esophagus or esophageal adenocarcinoma (OR, 1.06, 0.63-1.79 and OR, 1.27, 0.77-2.10, respectively). Conclusions: Alcohol consumption in early adulthood may lead to the development of reflux esophagitis. More recent alcohol consumption does not appear to confer any increased risk of reflux esophagitis, Barrett's esophagus, or esophageal adenocarcinoma. In fact, wine consumption may reduce the risk of these 3 esophageal disorders.

Abnormal integrity of association fiber tracts in amnestic mild cognitive impairment.

The association fiber tracts integrity of the inter-hemispheric and within-hemispheric communication was poor understood in amnestic type mild cognitive impairment (aMCI) patients by diffusion tensor imaging (DTI). A region of interest-based DTI approach was applied to explore fiber tract differences between 22 aMCI patients and 22 well-matched normal aging. Correlations were also sought between fractional anisotropy (FA) values and the cognitive performance scores in the aMCI patients. Extensive impairment of association fiber tracts integrity was observed in aMCI patients, including bilateral inferior fronto-occipital fascicles, the genu of corpus callosum, bilateral cingulate bundles and bilateral superior longitudinal fascicles II (SLE II) subcomponent. In addition, the FA value of right SLE II was significantly negatively correlated to the performance of Trail Making Test A and B, whilst the values of right posterior cingulate bundle was significantly positive correlation with MMSE score. As aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), this study suggested that investigation of association fiber tracts between remote cortexes may yield important new data to predict whether a patient will eventually develop AD.

Association between breastfeeding and anthropometry and cardiovascular disease risk factor status in adolescence and young adulthood: the Young Hearts Project, Northern Ireland.

Objective: To examine the association between breastfeeding and blood pressure, anthropometry, and plasma lipid profile in both adolescence and young adulthood. Design: Longitudinal study of biological and behavioural risk factors for cardiovascular disease. Setting: The Young Hearts Project, Northern Ireland Subjects: School children aged 12 years and 15 years who participated in a cross-sectional study of lifestyle and health, and who were followed up as young adults aged 20 – 25 years. Results: There was no significant difference in height, weight, BMI, skin-fold thickness measurements, blood pressure or plasma lipid profile in adolescents who had been breastfed when compared to those who had not been breastfed. However, by the time these adolescents had reached adulthood, those who had been breastfed were significantly taller when compared to those who had not been breastfed (standing height, P=0.013; leg length (P=0.035)). Specifically, the breastfed group were on average taller by 1.7cm (95% CI 0.4, 3.0) and had longer legs by 1cm (95% CI 0.1, 1.9). There was no significant difference in other anthropometric measures, blood pressure or plasma lipid profile in adults who had been breastfed when compared to those who had not been breastfed. Conclusions: Compared with those who had not been breastfed, individuals who had been breastfed were taller in adulthood. Given the known association of increased adult height with improved life expectancy the results from this study support a beneficial effect of breastfeeding.

The Association Between Childhood Trauma and Memory Functioning in Schizophrenia

Objective: Both neurocognitive impairments and a history of childhood abuse are highly prevalent in patients with schizophrenia. Childhood trauma has been associated with memory impairment as well as hippocampal volume reduction in adult survivors. The aim of the following study was to examine the contribution of childhood adversity to verbal memory functioning in people with schizophrenia. Methods: Eighty-five outpatients with a Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) diagnosis of chronic schizophrenia were separated into 2 groups on the basis of self-reports of childhood trauma. Performance on measures of episodic narrative memory, list learning, and working memory was then compared using multivariate analysis of covariance. Results: Thirty-eight (45%) participants reported moderate to severe levels of childhood adversity, while 47 (55%) reported no or low levels of childhood adversity. After controlling for premorbid IQ and current depressive symptoms, the childhood trauma group had significantly poorer working memory and episodic narrative memory. However, list learning was similar between groups. Conclusion: Childhood trauma is an important variable that can contribute to specific ongoing memory impairments in schizophrenia.

Association of gene expression with sequential proliferation, differentiation and tumor formation in murine skin

Differential gene expression in two established initiation and promotion skin carcinogenesis models during promotion and tumor formation was determined by microarray technology with the purpose of distinguishing the genes more associated with neoplastic transformation from those linked with proliferation and differentiation. The first model utilized dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol 13-acetate (TPA) promotion in the FVB/N mouse, and the second TPA promotion of the Tg.Ac mouse, which is endogenously initiated by virtue of an activated Ha-ras transgene. Comparison of gene expression profiles across the two models identified genes whose altered expression was associated with papilloma formation rather than TPA-induced proliferation and differentiation. DMBA suppressed TPA-induced differentiation which allowed identification of those genes associated more specifically with differentiation rather than proliferation. EASE (Expression Analysis Systemic Explorer) indicated a correlation between muscle-associated genes and skin differentiation, whereas genes involved with protein biosynthesis were strongly correlated with proliferation. For verification the altered expression of selected genes were confirmed by RT-PCR; Carbonic anhydrase 2, Thioredoxin 1 and Glutathione S-transferase omega 1 associated with papilloma formation and Enolase 3, Cystatin 6 and Filaggrin associated with TPA-induced proliferation and differentiation. In situ analysis located the papillomas Glutathione S-transferase omega 1 expression to the proliferating areas of the papillomas. Thus we have identified profiles of differential gene expression associated with the tumorigenesis and promotion stages for skin carcinogenesis in the mouse.