Vaspin (SERPINA12) genotypes and risk of type 2 diabetes: Results from the MONICA/KORA studies.

Vaspin has recently been identified as novel adipokine with high expression in adipose tissue of obese and type 2 diabetic subjects and with potentially insulin-sensitising properties. However, the impact of vaspin gene variants on the risk of type 2 diabetes mellitus (T2DM) has not been determined yet. Therefore, the aim of our study was to investigate the association of vaspin single nucleotide polymorphisms (SNPs) with T2DM and obesity.

Meta-analysis of determinants for pet ownership in 12 European birth cohorts on asthma and allergies: a GA2LEN initiative.

Background: Studies on pet ownership as a risk or protective factor for asthma and allergy show inconsistent results. This may be on account of insufficient adjustment of confounding factors.

Aim: The objective of this study was to describe determinants of cat and dog ownership in European families with and without allergies.

Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.

Background: Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.

Methods: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level.

Correlation between genetic and geographic structure in Europe.

Understanding the genetic structure of the European population is important, not only from a historical perspective, but also for the appropriate design and interpretation of genetic epidemiological studies. Previous population genetic analyses with autosomal markers in Europe either had a wide geographic but narrow genomic coverage [1, 2], or vice versa [3-6]. We therefore investigated Affymetrix GeneChip 500K genotype data from 2,514 individuals belonging to 23 different subpopulations, widely spread over Europe.

Informatics and medicine--from molecules to populations.

Objectives: To clarify challenges and research topics for informatics in health and to describe new approaches for interdisciplinary collaboration and education.

Methods: Research challenges and possible solutions were elaborated by scientists of two universities using an interdisciplinary approach, in a series of meetings over several months.

Results And Conclusion: In order to translate scientific results from bench to bedside and further into an evidence-based and efficient health system, intensive collaboration is needed between experts from medicine, biology, informatics, engineering, public health, as well as social and economic sciences.

We and our pets: allergic together?

The study of allergies in creatures living together without being relatives can help us understand the impact of environmental influences. We tested the association of allergies in humans and their pets. A nested unmatched case-control study was performed in a random sample of 4261 inhabitants, aged 25-74 years, of the City of Augsburg, Germany and two adjacent counties.

PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome.

We identified association of restless legs syndrome (RLS) with PTPRD at 9p23-24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5' UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, P(nominal/lambda corrected) = 5.91 x 10(-10), odds ratio (OR) = 1.

Population attributable fraction for lung cancer due to residential radon in Switzerland and Germany.

Studies on miners as well as epidemiological studies in the general population show an increased lung cancer risk after exposure to radon and its progeny. The European pooled analysis of indoor radon studies estimates an excess relative risk of 8% (16% after correction for measurement uncertainties) per 100 Bq m(-3) indoor radon concentration. Here, we determine the population attributable fraction (PAF) for lung cancer due to residential radon based on this risk estimate for Switzerland and Germany.

Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 genes confer risk of type 2 diabetes independently of BMI in the German KORA studies.

Genome-wide association (GWA) studies identified novel gene variants that are associated with type 2 diabetes. However, results were not always consistent across different populations. Thus, the aims of this study were (i) to replicate findings from previous GWA studies in mainly Northern European populations using data from the German KORA 500 K diabetes project and (ii) to assess the impact of BMI on associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes.

Genetic variants in the USF1 gene are associated with low-density lipoprotein cholesterol levels and incident type 2 diabetes mellitus in women: results from the MONICA/KORA Augsburg case-cohort study, 1984-2002.

Objective: Upstream transcription factor 1 (USF1) regulates genes of glucose and lipid metabolism. Polymorphisms in the USF1 gene showed association with familial combined hyperlipidemia and lipid parameters. The aim of our study was to examine the associations between USF1 polymorphisms and lipid parameters as well as incident type 2 diabetes mellitus (T2DM) in German Caucasians.

Preventive effect of hydrolyzed infant formulas persists until age 6 years: long-term results from the German Infant Nutritional Intervention Study (GINI).

Background: The long-term effect of nutritional intervention with hydrolyzed infant formulas on allergy development has not been sufficiently evaluated.

Objective: We performed a follow-up of the German Infant Nutritional Intervention study until 6 years of life to investigate the long-term allergy-preventive effect of 3 hydrolyzed infant formulas compared with cow's milk formula (CMF) in a randomized, double-blind trial.

Methods: Between 1995 and 1998, 2252 newborns with atopic heredity were randomly assigned at birth to receive one of 4 blinded formulas: partially or extensively hydrolyzed whey formula, extensively hydrolyzed casein formula, or CMF as milk substitute for the first 4 months when breast-feeding was insufficient.

Intensity of physical exertion and triggering of myocardial infarction: a case-crossover study.

Aims: Acute myocardial infarction (AMI) can be precipitated or triggered by discrete transient exposures including physical exertion. We evaluated whether the risk of having an AMI triggered by physical exertion exhibits an exposure-response relationship, and whether it varies by ambient temperature or by taking place indoors or outdoors.

Methods And Results: We conducted a case-crossover study within the Myocardial Infarction Registry in Augsburg, Germany in 1999-2003.

Spatial and temporal variation of particle number concentration in Augsburg, Germany.

Epidemiological studies on health effects of outdoor air pollution are largely based on a single monitoring site to estimate the exposure of people living in urban areas. For such an approach two aspects are important: the temporal correlation and the spatial variation of the absolute levels of concentrations measured at different sites in an urban area. Whereas many studies have shown small spatial variability of fine particles in urban areas, little is known on how well a single monitoring station could represent the temporal and spatial variation of ultrafine particles across urban areas.

Matrix metalloproteinase 1 (MMP1) is associated with early-onset lung cancer.

Matrix metalloproteinases (MMP) play a key role in the breakdown of extracellular matrix and in inflammatory processes. MMP1 is the most highly expressed interstitial collagenase degrading fibrillar collagens. Overexpression of MMP1 has been shown in tumor tissues and has been suggested to be associated with tumor invasion and metastasis.

Sodium channel β1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans.

Brugada syndrome is a genetic disease associated with sudden cardiac death that is characterized by ventricular fibrillation and right precordial ST segment elevation on ECG. Loss-of-function mutations in SCN5A, which encodes the predominant cardiac sodium channel alpha subunit NaV1.5, can cause Brugada syndrome and cardiac conduction disease.

Common variants near MC4R are associated with fat mass, weight and risk of obesity.

To identify common variants influencing body mass index (BMI), we analyzed genome-wide association data from 16,876 individuals of European descent. After previously reported variants in FTO, the strongest association signal (rs17782313, P = 2.9 x 10(-6)) mapped 188 kb downstream of MC4R (melanocortin-4 receptor), mutations of which are the leading cause of monogenic severe childhood-onset obesity.

Source apportionment of ambient fine particle size distribution using positive matrix factorization in Erfurt, Germany.

Particle size distribution data collected between September 1997 and August 2001 in Erfurt, Germany were used to investigate the sources of ambient particulate matter by positive matrix factorization (PMF). A total of 29,313 hourly averaged particle size distribution measurements covering the size range of 0.01 to 3.

Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene.

The polymorphism SNP309 (rs2279744) in the promoter region of the MDM2 gene has been shown to alter protein expression and may play a role in the susceptibility to lung cancer. The MDM2 protein is a key inhibitor of p53 and several mechanisms of MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth and apoptosis.We used 635 Caucasian patients diagnosed with lung cancer before 51 years of age and 1300 healthy gender and age frequency matched population Caucasian controls to investigate the association between the MDM2 SNP309 and the risk of developing early onset lung cancer.

Quantifying the contribution of genetic variants for survival phenotypes.

Particularly in studies based on population representative samples, it is of major interest what impact a genetic variant has on the phenotype of interest, which cannot be answered by mere association estimates alone. One possible measure for quantifying the phenotype's variance explained by the genetic variant is R(2). However, for survival outcomes, no clear definition of R(2) is available in the presence of censored observations.

Identification of ten loci associated with height highlights new biological pathways in human growth.

Height is a classic polygenic trait, reflecting the combined influence of multiple as-yet-undiscovered genetic factors. We carried out a meta-analysis of genome-wide association study data of height from 15,821 individuals at 2.2 million SNPs, and followed up the strongest findings in >10,000 subjects.

On the replication of genetic associations: timing can be everything!

The failure of researchers to replicate genetic-association findings is most commonly attributed to insufficient statistical power, population stratification, or various forms of between-study heterogeneity or environmental influences.(1) Here, we illustrate another potential cause for nonreplications that has so far not received much attention in the literature. We illustrate that the strength of a genetic effect can vary by age, causing "age-varying associations.

Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.

Background: Recently, genome-wide association studies identified variants on chromosome 9p21.3 as affecting the risk of coronary artery disease (CAD). We investigated the association of this locus with CAD in 7 case-control studies and undertook a meta-analysis.

Atopic diseases, allergic sensitization, and exposure to traffic-related air pollution in children.

Rationale: In vitro studies, animal experiments, and human exposure studies have shown how ambient air pollution increases the risk of atopic diseases. However, results derived from observational studies are inconsistent.

Objectives: To assess the relationship between individual-based exposure to traffic-related air pollutants and allergic disease outcomes in a prospective birth cohort study during the first 6 years of life.

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.

Genetic variation in soluble epoxide hydrolase (EPHX2) is associated with an increased risk of ischemic stroke in white Europeans.

Background And Purpose: Genetic variation in the EPHX2 gene region has been reported to influence susceptibility to ischemic stroke in blacks. We assessed the role of this gene region in white Europeans and performed analyses with regard to stroke subtypes.

Methods: Twenty-six single nucleotide polymorphisms in the EPHX2 gene region were genotyped in 601 patients with ischemic stroke and 736 matched controls.