Noninvasive diagnosis of urothelial cancer in urine using DNA hypermethylation signatures-Gender matters.

Urothelial cancer (UCa) is the most predominant cancer of the urinary tract and noninvasive diagnosis using hypermethylation signatures in urinary cells is promising. Here, we assess gender differences in a newly identified set of methylation biomarkers. UCa-associated hypermethylated sites were identified in urine of a male screening cohort (n = 24) applying Infinium-450K-methylation arrays and verified in two separate mixed-gender study groups (n = 617 in total) using mass spectrometry as an independent technique.

Strategies for validation and testing of DNA methylation biomarkers.

DNA methylation is a stable covalent epigenetic modification of primarily CpG dinucleotides that has recently gained considerable attention for its use as a biomarker in different clinical settings, including disease diagnosis, prognosis and therapeutic response prediction. Although the advent of genome-wide DNA methylation profiling in primary disease tissue has provided a manifold resource for biomarker development, only a tiny fraction of DNA methylation-based assays have reached clinical testing. Here, we provide a critical overview of different analytical methods that are suitable for biomarker validation, including general study design considerations, which might help to streamline epigenetic marker development.

No association between genetic or epigenetic variation in insulin growth factors and antipsychotic-induced metabolic disturbances in a cross-sectional sample.

Aim: Second-generation antipsychotics (SGA) are known to induce metabolic disturbances. Genetic pathways, such as the IGF pathway could be associated with increased metabolic syndrome (MetS). Additionally, IGF2 methylation varies as a function of environmental influences and is associated with schizophrenia and MetS.

Stemness of the organ of Corti relates to the epigenetic status of Sox2 enhancers.

In the adult mammalian auditory epithelium, the organ of Corti, loss of sensory hair cells results in permanent hearing loss. The underlying cause for the lack of regenerative response is the depletion of otic progenitors in the cell pool of the sensory epithelium. Here, we show that an increase in the sequence-specific methylation of the otic Sox2 enhancers NOP1 and NOP2 is correlated with a reduced self-renewal potential in vivo and in vitro; additionally, the degree of methylation of NOP1 and NOP2 is correlated with the dedifferentiation potential of postmitotic supporting cells into otic stem cells.

Quantitative methylation analysis of HOXA3, 7, 9, and 10 genes in glioma: association with tumor WHO grade and clinical outcome.

Purpose: The purpose of this study was to determine whether specific HOXA epigenetic signatures could differentiate glioma with distinct biological, pathological, and clinical characteristics.

Methods: We evaluated HOXA3, 7, 9, and 10 methylation in 63 glioma samples by MassARRAY and pyrosequencing.

Results: We demonstrated the direct statistical correlation between the level of methylation of all HOXA genes examined and WHO grading.

Association study between variants in the fibrinogen gene cluster, fibrinogen levels and hypertension: results from the MONICA/KORA study.

Previous studies reported a gender-specific association between plasma fibrinogen concentrations and incident hypertension. We systematically analysed polymorphisms and haplotypes across the fibrinogen gene cluster with fibrinogen levels and assessed their contribution to prevalent hypertension in 2,200 men and 2,159 women from the population-based MONICA/KORA Augsburg study. Eleven tagging single nucleotide polymorphisms (SNPs) were systematically selected in the three fibrinogen genes and haplotypes were reconstructed.

Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus.

High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait.

Joint analysis of individual participants' data from 17 studies on the association of the IL6 variant -174G>C with circulating glucose levels, interleukin-6 levels, and body mass index.

Background: Several studies have investigated associations between the -174G>C single nucleotide polymorphism (rs1800795) of the IL6 gene and phenotypes related to type 2 diabetes mellitus (T2DM) but presented inconsistent results.

Aims: This joint analysis aimed to clarify whether IL6 -174G>C was associated with glucose and circulating interleukin-6 concentrations as well as body mass index (BMI).

Methods: Individual-level data from all studies of the IL6-T2DM consortium on Caucasian subjects with available BMI were collected.

SLC30A8 (ZnT8) Polymorphism is Associated with Young Age at Type 1 Diabetes Onset.

It was recently shown that the major allele of the SLC30A8 (zinc transporter 8, ZnT8) single nucleotide polymorphism (SNP) rs13266634 was associated with type 2 diabetes and with reduced insulin secretion in non-diabetic relatives. Because of its role in beta-cell function, we hypothesized that this candidate SNP may confer increased susceptibility for beta-cell destruction in type 1 diabetes. We analyzed SLC30A8 genotypes in 874 patients with type 1 diabetes and 1021 control subjects.

SLC2A9 influences uric acid concentrations with pronounced sex-specific effects.

Serum uric acid concentrations are correlated with gout and clinical entities such as cardiovascular disease and diabetes. In the genome-wide association study KORA (Kooperative Gesundheitsforschung in der Region Augsburg) F3 500K (n = 1,644), the most significant SNPs associated with uric acid concentrations mapped within introns 4 and 6 of SLC2A9, a gene encoding a putative hexose transporter (effects: -0.23 to -0.

Sample selection algorithm to improve quality of genotyping from plasma-derived DNA: to separate the wheat from the chaff.

Plasma and serum samples were often the only biological material collected for earlier epidemiological studies. These studies have a huge informative content, especially due to their long follow-up and would be an invaluable treasure for genetic investigations. However, often no banked DNA is available.

Association of prostaglandin E synthase 2 (PTGES2) Arg298His polymorphism with type 2 diabetes in two German study populations.

Context: On the basis of its chromosomal localization and its role in the synthesis of the antilipolytic compound prostaglandin E(2), the prostaglandin E synthase 2 (PTGES2) is a candidate gene for type 2 diabetes.

Objective: The aim of the present study was to investigate whether genetic variants in the PTGES2 gene are associated with type 2 diabetes.

Results: Sequencing of the PTGES2 gene revealed one nonsynonymous coding single-nucleotide polymorphism (SNP) (Arg298His, rs13283456) and a previously unknown promoter SNP g.

Association of acyl-CoA-binding protein (ACBP) single nucleotide polymorphisms and type 2 diabetes in two German study populations.

The human acyl-CoA-binding protein (ACBP) is a potential candidate gene of type 2 diabetes (T2D), since it plays a central role in determining the intracellular concentration of activated fatty acids which contribute to insulin resistance. The aim of our study was to evaluate whether single nucleotide polymorphisms (SNPs) of the ACBP gene are associated with risk of T2D. Genotyping of eight SNPs (rs2084202, rs3731607, rs8192501, rs8192504, rs2244135, rs2276596, rs8192506, rs2289948) was performed in 192 incident T2D subjects and 384 matched controls of the European Prospective Investigation into Cancer and Nutrition-Potsdam cohort.

Weak independent association signals between IDE polymorphisms, Alzheimer's disease and cognitive measures.

Functional and genetic studies suggest that insulin-degrading enzyme (IDE) may be a strong functional and positional candidate. As there is a lack of consensus in regards to the level and location of IDE association signals we aimed to clarify these discrepancies through genotyping 28 SNPs in a large case-control collective together with quantitative measures of cognitive ability (MMSE). Four SNPs (rs11187007, rs2149632_ide12, rs11187033, rs11187040) were found to be associated with AD (nominal p<0.

Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids.

Fatty acid composition in membranes plays an important role in cellular processes and has shown to be associated with the aetiology of several complex diseases in humans. We report strong associations between variants in the human delta-5 and delta-6 desaturase genes FADS1 FADS2 and fatty acid composition in serum phospholipids. Eighteen polymorphisms located in this gene cluster were genotyped in 727 adults from Erfurt, a German centre of the European Community Respiratory Health Survey.

Genetic architecture of the APM1 gene and its influence on adiponectin plasma levels and parameters of the metabolic syndrome in 1,727 healthy Caucasians.

The associations of the adiponectin (APM1) gene with parameters of the metabolic syndrome are inconsistent. We performed a systematic investigation based on fine-mapped single nucleotide polymorphisms (SNPs) highlighting the genetic architecture and their role in modulating adiponectin plasma concentrations in a particularly healthy population of 1,727 Caucasians avoiding secondary effects from disease processes. Genotyping 53 SNPs (average spacing of 0.

The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians.

Low concentrations of adiponectin, the protein product of the APM1 gene, have been reported to be associated with obesity and insulin resistance. However, contrasting results have been described on the genetic variability in APM1 and characteristics of the metabolic syndrome and adiponectin serum concentrations. In the present study, we investigated the association of the two most well-known SNPs of APM1 (+45T>G and +276G>T) and their haplotypes, with serum adiponectin concentrations, metabolic parameters and intima-media thickness of the carotid arteries in 1,745 well-phenotyped asymptomatic unrelated Caucasian subjects of the SAPHIR cohort.

Association of the interleukin-1 receptor antagonist gene with asthma.

The interleukin-1 cluster on human chromosome 2q12-2q14 harbors various promising candidate genes for asthma and other inflammatory diseases. We conducted a systematic association study with single-nucleotide polymorphisms (SNPs) located in candidate genes situated in this cluster. Single-marker, two-locus and three-locus haplotype analysis of SNPs yielded several significant results (p < 0.

High-resolution SNP scan of chromosome 6p21 in pooled samples from patients with complex diseases.

We apply a high-throughput protocol of chip-based mass spectrometry (matrix-assisted laser desorption/ionization time-of-flight; MALDI-TOF) as a method of screening for differences in single-nucleotide polymorphism (SNP) allele frequencies. Using pooled DNA from individuals with asthma, Crohn's disease (CD), schizophrenia, type 1 diabetes (T1D), and controls, we selected 534 SNPs from an initial set of 1435 SNPs spanning a 25-Mb region on chromosome 6p21. The standard deviations of measurements of time of flight at different dots, from different PCRs, and from different pools indicate reliable results on each analysis step.