Friedrich Heiler, die „Hochkirche“ und die völkische Bewegung

Friedrich Heiler, the “High Church” and the “völkisch” movement. – The term “people” is not by nature a key word in the work of the religious scholar and theologian Friedrich Heiler (1892–1967). In his book “Gebet” (Prayer) and in the other major works of the 1920s, it is encountered rather casually. The forced confrontation with it is all the more important as the term was highly politicised in the early 1930s. A thematic issue of the journal “Hochkirche” on the subject of “Church and People” (July/August 1933) shows the inner tensions to which the High Church movement was exposed. Heiler’s attempt to preserve the concept as a genuinely theological term was, on the one hand, doomed to failure in the short term, but on the other hand contributed to the movement’s ability to endure and survive

Nocturnal hypoxemic burden and micro- and macrovascular disease in patients with type 2 diabetes

Background Micro- and macrovascular diseases are common in patients with type 2 diabetes mellitus (T2D) and may be partly caused by nocturnal hypoxemia. The study aimed to characterize the composition of nocturnal hypoxemic burden and to assess its association with micro- and macrovascular disease in patients with T2D. Methods This cross-sectional analysis includes overnight oximetry from 1247 patients with T2D enrolled in the DIACORE (DIAbetes COhoRtE) study. Night-time spent below a peripheral oxygen saturation of 90% (T90) as well as T90 associated with non-specific drifts in oxygen saturation (T90non − specific), T90 associated with acute oxygen desaturation (T90desaturation) and desaturation depths were assessed. Binary logistic regression analyses adjusted for known risk factors (age, sex, smoking status, waist-hip ratio, duration of T2D, HbA1c, pulse pressure, low-density lipoprotein, use of statins, and use of renin-angiotensin-aldosterone system inhibitors) were used to assess the associations of such parameters of hypoxemic burden with chronic kidney disease (CKD) as a manifestation of microvascular disease and a composite of cardiovascular diseases (CVD) reflecting macrovascular disease. Results Patients with long T90 were significantly more often affected by CKD and CVD than patients with a lower hypoxemic burden (CKD 38% vs. 28%, p < 0.001; CVD 30% vs. 21%, p < 0.001). Continuous T90desaturation and desaturation depth were associated with CKD (adjusted OR 1.01 per unit, 95% CI [1.00; 1.01], p = 0.008 and OR 1.30, 95% CI [1.06; 1.61], p = 0.013, respectively) independently of other known risk factors for CKD. For CVD there was a thresholdeffect, and only severly and very severly increased T90non−specific was associated with CVD ([Q3;Q4] versus [Q1;Q2], adjusted OR 1.51, 95% CI [1.12; 2.05], p = 0.008) independently of other known risk factors for CVD. Conclusion While hypoxemic burden due to oxygen desaturations and the magnitude of desaturation depth were significantly associated with CKD, only severe hypoxemic burden due to non-specific drifts was associated with CVD. Specific types of hypoxemic burden may be related to micro- and macrovascular disease

Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins

Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23 274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m2) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 × 10−7), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 × 10−6) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 × 10−4). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoprotein

Functional Characterization of Promoter Variants of the Adiponectin Gene Complemented by Epidemiological Data

# These authors contributed equally to the work. *Corresponding author

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

Copyright: Copyright 2008 Elsevier B.V., All rights reserved.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 0.7 kb) in the APM1 gene region in 81 Caucasians revealed a two-block linkage disequilibrium (LD) structure and enabled comprehensive tag SNP selection. We found particularly strong associations with adiponectin concentrations for 11 of the 15 tag SNPs in the 1,727 subjects (five P values <0.0001). Haplotype analysis provided a thorough differentiation of adiponectin concentrations with 9 of 17 haplotypes showing significant associations (three P values <0.0001). No significant association was found for any SNP with the parameters of the metabolic syndrome. We observed a two-block LD structure of APM1 pointing toward at least two independent association signals, one including the promoter SNPs and a second spanning the relevant exons. Our data on a large number of healthy subjects suggest a clear modulation of adiponectin concentrations by variants of APM1, which are not merely a concomitant effect in the course of type 2 diabetes or coronary artery disease.publishersversionPeer reviewe

Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

INTRODUCTION: Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. METHODS: In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. RESULTS: The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m(2) but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. DISCUSSION: We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.