Genome-Wide Association Studies of Alcohol Depende... [Curr Psychiatry Rep. 2011] - PubMed result

Curr Psychiatry Rep. 2011 Jan 21. [Epub ahead of print]

Genome-Wide Association Studies of Alcohol Dependence and Substance Use Disorders.
Treutlein J, Rietschel M.

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health Mannheim (CIMH), University of Heidelberg, J5, 68159, Mannheim, Germany,

jens.treutlein@zi-mannheim.de.

Abstract

Genome-wide association studies (GWAS) currently represent the most systematic approach to genetic research into complex disorders. They can detect associations of common variants in genomic regions in the absence of an a priori assumption. Most of the GWAS of addiction performed to date have focused on alcohol dependence or smoking behavior. Four GWAS of alcohol dependence have been published thus far, and only two single nucleotide polymorphisms have received modest support of replication in a subsequent study. Many more GWAS have been conducted for smoking behavior. One large, single GWAS and meta-analyses of the phenotype “smoking quantity” have generated convincing evidence for the contribution of variants in genes for cholinergic nicotinic receptor subunits. This article focuses on GWAS of alcohol addiction and provides an overview of GWAS of other substance abuse disorders.

PMID: 21253885 [PubMed - as supplied by publisher]
Genome-Wide Association Studies of Alcohol Depende… [Curr Psychiatry Rep. 2011] – PubMed result

Metabolic Syndrome: From the Genetics to the Patho... [Curr Hypertens Rep. 2010] - PubMed result

Curr Hypertens Rep. 2010 Oct 19. [Epub ahead of print]
Metabolic Syndrome: From the Genetics to the Pathophysiology.

Sookoian S, Pirola CJ.

Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari – IDIM, University of Buenos Aires – National Council of Scientific and Technological Research (CONICET), Av. Combatiente de Malvinas 3150, (C1427ARO), Ciudad Autonoma de Buenos Aires, Argentina

, ssookoian@lanari.fmed.uba.ar.

Abstract

The metabolic syndrome (MS) constitutes a combination of underlying risk factors for an adverse outcome, cardiovascular disease. Thus, the clinical behavior of the MS can be regarded as a whole. Nevertheless, from a pathogenic point of view, understanding of the underlying mechanisms of each MS intermediate phenotype is far beyond their understanding as an integrative process. Systems biology introduces a new concept for revealing the pathogenesis of human disorders and suggests the presence of common physiologic processes and molecular networks influencing the risk of a disease. This paper shows a model of this concept to explain the genetic determinants of MS-associated phenotypes. Based on the hypothesis that common physiologic processes and molecular networks may influence the risk of MS disease components, we propose two systems-biology approaches: a gene enrichment analysis and the use of a protein-protein interaction network. Our results show that a network driven by many members of the nuclear receptor superfamily of proteins, including retinoid X receptor and farnesoid X receptor (FXR), may be implicated in the pathogenesis of the MS by its interactions at multiple levels of complexity with genes associated with metabolism, cell differentiation, and oxidative stress. In addition, we review two alternative genetic mechanisms that are gaining acceptance in the physiopathology of the MS: the regulation of transcriptional and post-transcriptional gene expression by microRNAs and epigenetic modifications such as DNA methylation.

PMID: 20957457 [PubMed - as supplied by publisher]
Metabolic Syndrome: From the Genetics to the Patho… [Curr Hypertens Rep. 2010] – PubMed result

Canadian Expert Group consensus recommendations: ... [Curr Oncol. 2011] - PubMed - NCBI

Curr Oncol. 2011 Aug;18(4):e180-4.

Canadian Expert Group consensus recommendations: KRAS testing in colorectal cancer.

Aubin F, Gill S, Burkes R, Colwell B, Kamel-Reid S, Koski S, Pollett A, Samson B, Tehfe M, Wong R, Young S, Soulières D.

Source

Centre Hospitalier de l’Université de Montréal, Montreal, QC.

Abstract

Monoclonal antibodies against the epidermal growth factor receptor (anti-egfr) when used in the treatment of metastatic colorectal cancer are associated with improved survival. Patients whose tumours harbor a KRAS mutation in codon 12 or 13 have been shown not to benefit from anti-egfr antibodies. The importance of KRAS mutation status in the management of patients with metastatic colorectal cancer has led to the elaboration of Canadian consensus recommendations on KRAS testing, with the aim of standardizing practice across Canada and reconciling testing access with the clinical demand for testing. The present guidelines were developed at a Canadian consensus meeting held in Montreal in April 2010. The best available evidence and expertise were used to develop recommendations for various aspects of KRAS testing, including indications and timing for testing, sample requirements, recommendations for reporting requirements, and acceptable turnaround times.

PMID:

21874108

[PubMed - in process]

PMCID: PMC3149550

Canadian Expert Group consensus recommendations: … [Curr Oncol. 2011] – PubMed – NCBI

Genome-Wide Association Studies: Is there a Genoty... [Curr Pharm Des. 2011] - PubMed result

Curr Pharm Des. 2011 Feb 28. [Epub ahead of print]

Genome-Wide Association Studies: Is there a Genotype for Cognitive Decline in Older Persons with Type 2 Diabetes?
Abbatecola AM, Oliveri F, Corsonello A, Antonicelli R, Corica F, Lattanzio F.

Italian National Research Center on Aging (INRCA), Scientific Direction, Ancona, Italy. angela_abbatecola@libero.it.

Abstract
There is a dramatic increase in the number of elderly persons on a worldwide scale with an increase in chronic comorbidities, especially type 2 diabetes (T2DM) and dementia. Although cognitive faculties commonly deteriorate in non-diabetic persons as they age, several studies have concluded that diabetes is uniquely associated with cognitive decline and is associated with a two-fold risk of Alzheimer’s Disease (AD). Studies have also suggested that good glycemic has shown to improve cognitive status, however whether the use of specific anti-diabetic oral agents may play an additional role in controlling against cognitive deterioration is unknown. In addition, excitotoxicity from the overstimulation of glutamate receptors is considered a major cause of neuron death in AD and statins may be promising agents for protecting against memory loss. Possible pathophysiologic mechanisms common to both T2DM and AD are glucose toxicity and a direct effect of insulin on amyloid metabolism. In fact, AD and T2DM have comparable pathological features in the islet and brain (amyloid derived from amyloid β protein (β-amyloid) in the brain in AD and islet amyloid derived from islet amyloid polypeptide in the pancreas in T2DM). Evidence is growing linking precursors of amyloid deposition in the brain and pancreas to the pathogenesis of AD and T2DM, respectively. Indeed, the need to identify agents capable of correcting such pathological features may in turn significantly protect against the accumulation of β-amyloid in the brain, known to interfere with correct cognitive function. Cholesterol may also be directly involved in β-amyloid aggregation: abnormal oxidative metabolites such as cholesterol-derived aldehydes can modify β-amyloid, firstly promoting Schiff base formation, then accelerating the early stages of amyloidogenesis. At the moment, genome-wide association studies (GWAS) have begun to elucidate the genetic architecture of chronic diseases including, T2DM and AD. Thus, one of the challenges for a successful GWAS in the future will be to identify a genotype in older persons with T2DM for good drug response, which in turn may protect against cognitive decline and AD. The literature has suggested that the use of insulin sensitizers and statins are correlated with a lower rate of cognitive decline in older persons. In this paper, we will explore recent findings regarding diverse single nucleotide polymorphisms from GWAS on T2DM, AD and both. We will also shed light on future pathways, as the basis of improving drug and diagnostics development for a better integration of genetic studies for precise drug-development focusing on the role of genetic variation in maintaining metabolic control and cognitive performance.

PMID: 21352095 [PubMed - as supplied by publisher]

Genome-Wide Association Studies: Is there a Genoty… [Curr Pharm Des. 2011] – PubMed result