MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients.

BackgroundUpregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients.MethodsWe assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease.ResultsA high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (-1306C>T) and MMP-9 (-1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification.ConclusionMMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients

MMP-2 geno-phenotype is prognostic for colorectal cancer survival, whereas MMP-9 is not.

The prognostic significance of single-nucleotide polymorphisms (SNPs) and tumour protein levels of MMP-2 and MMP-9 was evaluated in 215 colorectal cancer patients. Single-nucleotide polymorphism MMP-2(-1306T) and high MMP-2 levels were significantly associated with worse survival. Extreme tumour MMP-9 levels were associated with poor prognosis but SNP MMP-9(-1562C>T) was not. Tumour MMP levels were not determined by their SNP genotypes

Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation

This is the final version of the article. Available from Springer Nature via the DOI in this record.Raw data were submitted to the European Genome-phenome Archive (EGA) under accession EGAS00001001077.X-chromosome inactivation (XCI), i.e., the inactivation of one of the female X chromosomes, restores equal expression of X-chromosomal genes between females and males. However, ~10% of genes show variable degrees of escape from XCI between females, although little is known about the causes of variable XCI. Using a discovery data-set of 1867 females and 1398 males and a replication sample of 3351 females, we show that genetic variation at three autosomal loci is associated with female-specific changes in X-chromosome methylation. Through cis-eQTL expression analysis, we map these loci to the genes SMCHD1/METTL4, TRIM6/HBG2, and ZSCAN9. Low-expression alleles of the loci are predominantly associated with mild hypomethylation of CpG islands near genes known to variably escape XCI, implicating the autosomal genes in variable XCI. Together, these results suggest a genetic basis for variable escape from XCI and highlight the potential of a population genomics approach to identify genes involved in XCI.This research was financially supported by several institutions: BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO, numbers 184.021.007 and 184.033.111); the UK Medical Research Council; Wellcome (www.wellcome.ac.uk; [grant number 102215/2/13/2 to ALSPAC]); the University of Bristol to ALSPAC; the UK Economic and Social Research Council (www.esrc.ac.uk; [ES/N000498/1] to CR); the UK Medical Research Council (www.mrc.ac.uk; grant numbers [MC_UU_12013/1, MC_UU_12013/2 to JLM, CR]); the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ; the Wellcome Trust, Medical Research Council, European Union (EU), and the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London

No evidence for association between tau gene haplotypic variants and susceptibility to Creutzfeldt-Jakob disease

Contains fulltext : 52965.pdf ( ) (Open Access)BACKGROUND: A polymorphism at codon 129 of the prion protein gene (PRNP) is the only well-known genetic risk factor for Creutzfeldt-Jakob disease (CJD). However, there is increasing evidence that other loci outside the PRNP open reading frame might play a role in CJD aetiology as well. METHODS: We studied tau protein gene (MAPT) haplotypic variations in a population of sporadic and variant CJD patients. We tested 6 MAPT haplotype tagging SNPs (htSNPs) in a Dutch population-based sample of sporadic CJD (sCJD) patients and a cognitively normal control group of similar age distribution. We genotyped the same polymorphisms in two other sample groups of sCJD cases from Italy and the UK. In addition, we compared MAPT haplotypes between sCJD and variant CJD (vCJD) patients. RESULTS: Single locus and haplotype analyses did not detect any significant difference between sCJD cases and controls. When we compared MAPT haplotypes between sCJD and variant CJD (vCJD) patients, we found that two of them were represented differently (H1f: 8% in sCJD versus 2% in vCJD; H1j:1% in sCJD versus 7% in vCJD). However, these two haplotypes were rare in both groups of patients, and taking the small sample sizes into account, we cannot exclude that the differences are due to chance. None of the p-values remained statistically significant after applying a multiple testing correction. CONCLUSION: Our study shows no evidence for an association between MAPT gene variations and sCJD, and some weak evidence for an association to vCJD

Walk-ins seeking treatment at an emergency department or general practitioner out-of-hours service: a cross-sectional comparison

Background Emergency Departments (ED) in Switzerland are faced with increasing numbers of patients seeking non-urgent treatment. The high rate of walks-ins with conditions that may be treated in primary care has led to suggestions that those patients would best cared for in a community setting rather than in a hospital. Efficient reorganisation of emergency care tailored to patients needs requires information on the patient populations using the various emergency services currently available. The aim of this study is to evaluate the differences between the characteristics of walk-in patients seeking treatment at an ED and those of patients who use traditional out-of-hours GP (General Practitioner) services provided by a GP-Cooperative (GP-C). Methods In 2007 and 2009 data was collected covering all consecutive patient-doctor encounters at the ED of a hospital and all those occurring as a result of contacting a GP-C over two evaluation periods of one month each. Comparison was made between a GP-C and the ED of the Waid City Hospital in Zurich. Patient characteristics, time and source of referral, diagnostic interventions and mode of discharge were evaluated. Medical problems were classified according to the International Classification of Primary Care (ICPC-2). Patient characteristics were compared using non-parametric tests and multiple logistic regression analysis was applied to investigate independent determinants for contacting a GP-C or an ED. Results Overall a total of 2974 patient encounters were recorded. 1901 encounters were walk-ins and underwent further analysis (ED 1133, GP-C 768). Patients consulting the GP-C were significantly older (58.9 vs. 43.8 years), more often female (63.5 vs. 46.9%) and presented with non-injury related medical problems (93 vs. 55.6%) in comparison with patients at the ED. Independent determining factors for ED consultation were injury, male gender and younger age. Walk-in distribution in both settings was equal over a period of 24 hours and most common during daytime hours (65%). Outpatient care was predominant in both settings but significantly more so at the GP-C (79.9 vs. 85.7%). Conclusions We observed substantial differences between the two emergency settings in a non gate-keeping health care system. Knowledge of the distribution of diagnoses, their therapy, of diagnostic measures and of the factors which determine the patients' choice of the ED or the GP-C is essential for the efficient allocation of resources and the reduction of costs

Type 2 diabetes gene TCF7L2 polymorphism is not associated with fetal and postnatal growth in two birth cohort studies

Background: An inverse association between birth weight and the risk of developing type 2 diabetes (T2D) in adulthood has been reported. This association may be explained by common g

The Rotterdam Study: objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in the Netherlands. The study targets cardiovascular, neurological, ophthalmological and endocrine diseases. As of 2008 about 15,000 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in some 600 research articles and reports (see http://www.epib.nl/rotterdamstudy). This article gives the reasons for the study and its design. It also presents a summary of the major findings and an update of the objectives and methods