Search results for "polymorph"
showing 10 items of 2115 documents
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
2012
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10 -8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral…
The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients
2008
Background: Tacrolimus is a substrate of cytochrome P-450 (CYP) 3A enzyme and of the drug transporter ABCBl. We have investigated the effects of possible relevant CYP3A5 and ABCBl single nucleotide polymorphisms (SNPs) present in both donors and recipients on tacrolimus blood levels achieved in a population of 32 Caucasian liver transplant patients. Material/Methods: At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C0) were determined. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for gen-otyping CYP3A5*3 [6986A>G] as well as ABCBl at exons 21 [2677G>T] and 26 [3435C>T]. Results:87.5…
Large-scale gene-centric analysis identifies novel variants for coronary artery disease.
2011
Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants. We examined 49,094 genetic variants in ∼2,100 genes of cardiovascular relevance, using a customised gene array in 15,596 CAD cases and 34,992 controls (11,202 cases and 30,733 controls of European descent; 4,394 cases and 4,259 controls of South Asian origin). We attempted to replicate putative novel associations in an additional 17,121 CAD cases and 40,473 controls. Potential mechanisms through w…
Role of S128R polymorphism of E-selectin in colon metastasis formation.
2007
The extravasation of cancer cells is a key step of the metastatic cascade. Polymorphisms in genes encoding adhesion molecules can facilitate metastasis by increasing the strength of interaction between tumor and endothelial cells as well as impacting other properties of cancer cells. We investigated the Ser128Arg (a561c at the nucleotide level) polymorphism in the E-selectin gene in patients with metastatic colon cancer and its functional significance. Genotyping for a561c polymorphism was performed on 172 cancer patients and on an age-matched control population. The colon cancer group was divided into groups with (M+) and without observable metastasis (M−). For in vitro functional assays, …
Interleukin-10 and interleukin-18 promoter polymorphisms in an Italian cohort of patients with undifferentiated carcinoma of nasopharyngeal type.
2004
Purpose: Cytokines such as IL-10 and IL-18 seem to be involved in the inflammatory response of undifferentiated carcinoma of nasopharyngeal type (UCNT). The aim of this study was to evaluate the correlation between functional single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 and IL-18 genes and the virological and clinical characteristics in a large case series of Caucasian patients suffering from UCNT, a tumor regularly associated with the Epstein Barr Virus (EBV). Methods: Eighty-nine patients with histologically confirmed UCNT and 130 healthy donors were included in our study. DNA was examined for the polymorphisms of IL-10 gene at positions –1082, −819, −592 by dire…
Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.
2011
One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns—independent component analysis—to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify maj…
Neuroblastoma after Childhood: Prognostic Relevance of Segmental Chromosome Aberrations, ATRX Protein Status, and Immune Cell Infiltration
2014
AbstractNeuroblastoma (NB) is a common malignancy in children but rarely occurs during adolescence or adulthood. This subgroup is characterized by an indolent disease course, almost uniformly fatal, yet little is known about the biologic characteristics. The aim of this study was to identify differential features regarding DNA copy number alterations, α-thalassemia/mental retardation syndrome X-linked (ATRX) protein expression, and the presence of tumor-associated inflammatory cells. Thirty-one NB patients older than 10 years who were included in the Spanish NB Registry were considered for the current study; seven young and middle-aged adult patients (range 18-60 years) formed part of the c…
Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types
2015
BACKGROUND: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.METHODS: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cance…
Polymorphisms of pro-inflammatory genes and prostate cancer risk: a pharmacogenomic approach.
2009
In this paper, we consider the role of the genetics of inflammation in the pathophysiology of prostate cancer (PCa). This paper is not an extensive review of the literature, rather it is an expert opinion based on data from authors' laboratories on age-related diseases and inflammation. The aim is the detection of a risk profile that potentially allows both the early identification of individuals at risk for disease and the possible discovery of potential targets for medication. In fact, a major goal of clinical research is to improve early detection of age-related diseases, cancer included, by developing tools to move diagnosis backward in disease temporal course, i.e., before the clinical…
Influence of class M1 glutathione S-transferase (GST Mu) polymorphism on GST M1 gene expression level and tumor size in oral squamous cell carcinoma.
2010
Glutathione S-transferases (GST) are antioxidant enzymes and oxidative stress markers in oral carcinogenesis. They present a system of polymorphic proteins. Some variants are associated with increased sensitivity to toxic compounds, as it is known for the GSTM1-null variant allele. However, the influence of the GSTM1 allele variant genotype on GSTM1-mRNA quantity in oral squamous cell carcinoma (OSCC) and normal mucosa as well as the impact on prognosis remains unclear. The genotype for GSTM1 (mutation vs. wild type) was determined by polymerase chain reaction (PCR) using genomic DNA extracted from peripheral blood from 28 OSCC patients. From the same patients, 28 pairs of OSCC cells and no…