Ischemic Heart Disease in German Immigrants and Their Descendants in a Region of Southern Brazil: A Comparison of Initial Symptoms Reported between two Generations

Abstract Background Nothing is known about ischemic heart disease (IHD) in the Germans who emigrated to Brazil during the last century. Objective We sought to compare age at diagnosis and IHD manifestations between German immigrants and their first-generation descendants in the region of Blumenau, Brazil. Methods We reviewed medical records of hospitals in Blumenau. Comparison of the groups in the evaluation times was made by analysis of variance (ANOVA) with repeated measures, and comparison of two factors was made by two-way ANOVA. The level of significance was set at p <0.05. Results Study population comprised 68 patients who were born in Germany (group G) and 99 descendants (group D). Twenty-nine patients of group D had two German parents and 70 had one. Mean age at diagnosis was 66.8 ± 10.6 years, with a significant difference between the groups, four years higher in Group G than group D (69.0 ± 8.8 vs 65.4 ± 11.5 years old) (p = 0.025). There was no significant difference in risk factors or coronary angiography data between the groups. HDL cholesterol levels were significantly higher in group G than in group D (48.4 ± 11.1 mg/dL vs 43.3 ± 11.2 mg/dL, p = 0.005). Conclusion At the time of first IHD diagnosis, mean age of the group G was significantly higher than group D, with no differences between groups in sex, risk factors, LDL levels, or clinical and angiographic manifestations. An earlier manifestation of the disease could be part of lifestyle changes in descendants, in this population that mantained eating habits characterized by high saturated fat consumption.

The Hospital Anxiety and Depression Scale (HADS) applied to Ethiopian cancer patients.

Psychological distress is a common problem associated with cancer. The main objective of the present study was to test the Hospital Anxiety and Depression Scale (HADS) in a sample of Ethiopian cancer patients and to compare the results with those obtained from a sample in Germany. Data were collected from 256 cancer patients who visited the University of Gondar Hospital between January 2019 and June 2019 using the HADS, the European Organization for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30), and the Multidimensional Fatigue Inventory MFI-20. The reliability of the HADS was good, with Cronbach's α coefficients of 0.86 (anxiety), 0.85 (depression), and 0.91 (total scale). The Ethiopian cancer patients were more anxious (M = 7.9) and more depressed (M = 9.3) than the German patients (M = 6.8 for anxiety and M = 5.5 for depression). Only a weak level of measurement invariance was detected between the Ethiopian and the German sample. In the Ethiopian sample, anxiety and depression were associated with tumor stage (high levels in stage 4) and treatment (high levels for patients not receiving surgery and chemotherapy). Both anxiety and depression were significantly associated with all of the EORTC QLQ-C30 and MFI-20 scales. The HADS proved to be applicable for use with Ethiopian cancer patients. The high level of anxiety and depression present in that group indicates a need for psychosocial care.

A matched-pair analysis on survival and response rates between German and non-German cancer patients treated at a Comprehensive Cancer Center.

BACKGROUND: Research shows disparities in cancer outcomes by ethnicity or socio-economic status. Therefore, it is the aim of our study to perform a matched-pair analysis which compares the outcome of German and non-German (in the following described as 'foreign') cancer patients being treated at the Center for Integrated Oncology (CIO) Köln Bonn at the University Hospital of Bonn between January 2010 and June 2016. METHODS: During this time, 6314 well-documented patients received a diagnosis of cancer. Out of these patients, 219 patients with foreign nationality could be matched to German patients based on diagnostic and demographic criteria and were included in the study. All of these 438 patients were well characterized concerning survival data (Overall survival, Progression-free survival and Time to progression) and response to treatment. RESULTS: No significant differences regarding the patients' survival and response rates were seen when all German and foreign patients were compared. A subgroup analysis of German and foreign patients with head and neck cancer revealed a significantly longer progression-free survival for the German patients. Differences in response to treatment could not be found in this subgroup analysis. CONCLUSIONS: In summary, no major differences in survival and response rates of German and foreign cancer patients were revealed in this study. Nevertheless, the differences in progression-free survival, which could be found in the subgroup analysis of patients with head and neck cancer, should lead to further research, especially evaluating the role of infectious diseases like human papillomavirus (HPV) and Epstein-Barr virus (EBV) on carcinogenesis and disease progression.

Vitamin D status and its determinants in healthy pregnant women living in Switzerland in the first trimester of pregnancy.

OBJECTIVES: Our study aimed at assessing the prevalence and determinants of vitamin D deficiency (25-hydroxy-vitamin D [25(OH)D] < 20 ng/mL) in pregnant women in the first trimester living in Switzerland. METHODS: From September 2014 through December 2015, 204 pregnant women were conveniently recruited during their first clinical appointment at the Clinic of Obstetrics of the University Hospital Zurich (between week 6 and 12 of pregnancy). Blood samples were collected and a questionnaire focusing on lifestyle and skin colour was completed face-to-face with the responsible physician. Logistic regression analyses were performed with vitamin D status as dependent variable. RESULTS: 63.2% of the participating women were vitamin D deficient, and the median vitamin D concentration in the overall sample was 17.1 ng/mL [Q1, Q3: 9.78, 22.3]. The highest proportions of vitamin D deficiency were detected in women originating from Africa and Middle East (91.4% deficient, median vitamin D concentration of 10.7 ng/mL [Q1, Q3: 6.55, 14.45]) and from South-East Asia/Pacific (88.5% deficient, median vitamin D concentration of 8.4 ng/mL [Q1, Q3: 6.10, 14.88]). Multivariable logistic regression showed that significant risk factors of vitamin D deficiency were country of origin (women born in Switzerland and Germany had a lower risk than women born in other countries), smoking status (lower risk for former smokers) and intake of vitamin D supplements. CONCLUSIONS: Our results confirm a high prevalence of vitamin D deficiency in this Swiss cohort, in particular in women coming from Asian and African countries, and underline the importance of appropriate counseling and vitamin D supplementation in early pregnancy.

[Tinea barbae profunda due to Trichophyton mentagrophytes after journey to Thailand : Case report and review]. / Tinea barbae profunda durch Trichophyton mentagrophytes nach Thailand-Reise : Fallbeschreibung und Übersicht.

Tinea barbae represents a very rare dermatophytosis. We report on a tinea barbae profunda following a journey to Southeast Asia. After travel to Thailand, a businessman was affected by a foudroyant proceeding abscessing infection of the upper lip and beard area. The initial therapy with oral acyclovir and oral ciprofloxacin, which later was changed to ampicillin plus sulbactam, intravenously, was unsuccessful. In a biopsy sample, histologically, with Grocott-Gomori's methenamine silver stain, fungal mycelium was apparent in the tissue. Thereupon, terbinafine 250 mg was given for 4 weeks, topically, a 1% ciclopiroxolamine-containing cream. In fungal culture, T. mentagrophytes were found to grow. Meanwhile, the patient's German wife suffered from a tinea faciei. From skin scrapings from the cheek, T. mentagrophytes was also cultivated. This zoophilic dermatophyte was identical with other zoophilic strains of T. mentagrophytes currently found in Germany, which were also acquired in Thailand. The patient had contact with Thai female sex workers who must be considered as a source of infection of the dermatophytosis. There was no animal contact, neither in Thailand, nor in Germany. The infection chain of the dermatophytosis from Thailand probably reached from a female sex worker via the here described patient to his wife in Germany. This pathway of infection has been known for 1 or 2 years, but until now, in Germany, Switzerland, and Austria exclusively via pubogenital infections (tinea genitalis profunda) due to T. mentagrophytes after journeys to Southeast Asia. For treatment, oral antifungal agents should be used, first of all terbinafine, alternatively fluconazole or itraconazole.

[Palliative care for patients with Turkish or Arabic migration background in Lower Saxony : A survey from palliative care professionals' perspective]. / Palliative Versorgung von Menschen mit türkischem oder arabischem Migrationshintergrund in Niedersachsen : Eine Befragung spezialisierter Palliativversorger.

BACKGROUND AND OBJECTIVES: People with a migration background (MB) are an important part of German society. If and how they use specialised palliative care (SPC) has not been studied. We aimed to assess the current SPC for patients with Turkish or Arabic MB (the largest group of immigrants in Germany with a shared ascribed culture) from the point of view of healthcare professionals (HCP) in Lower Saxony. METHOD: All HCPs in institutions providing SPC (n = 90) were invited to participate in an anonymous online survey which contained closed and open questions about care for this patient group, characteristics of the last patient with Turkish or Arabic MB they cared for, and resources and strategies to care for these patients. The survey was analysed using descriptive statistics and qualitative content analysis. RESULTS: Fifty-five HCPs in SPC participated, mostly nurses aged between 40 and 60 years. One fifth had not cared for a patient with Turkish or Arabic MB during the last 12 months. Given their local population, 84.6% estimated that they cared for a lower number of patients than would be representative. In care, problems with communication as well as difficulties to interact with and manage families, and in organising and planning care were most prevalent. Only 21% of participants had access to interpreters. DISCUSSION: Patients with Turkish or Arabic MB seem to be underrepresented in SPC. The high rate of communication problems highlights the necessity of reliable and accessible interpreter services. Most difficulties were of psychosocial nature, showing how important the holistic approach of SPC is in caring for terminally ill patients with Turkish or Arabic MB.

A social network analysis of substance use among immigrant adolescents in six European cities.

BACKGROUND: Social integration and the health of adolescents with a migration background is a major concern in multicultural societies. The literature, however, has paid little attention to the wider determinants of their health behaviours, including the composition of their social networks. The aim of this study was to describe the composition of adolescents' social networks according to migration background, and to examine how social networks are associated with substance use. METHOD: In 2013, the SILNE study surveyed 11,015 secondary-school adolescents in 50 schools in six European cities in Belgium, Finland, Germany, Italy, the Netherlands, and Portugal, using a social network design. Each adolescent nominated up to five of their best and closest friends. Migration status was defined as first-generation migrants, second-generation migrants, and speaking another language at home. We computed two groups of network structural positions, the centrality of individual adolescents in networks, and the homophily of their social ties regarding migration (same-migration). Multilevel logistic regression was used to model the association between network structural position and smoking, alcohol use, and cannabis use. RESULTS: Compared with non-migrant adolescents, adolescents with migration backgrounds had similar relationship patterns. But almost half their social ties were with same-migration-background adolescents; non-migrants had few social ties to migrants. For adolescents with a migration background, a higher proportion of social ties with non-migrants was associated with increased use of cannabis (OR = 1.07, p = 0.03) and alcohol (OR = 1.08, p < 0.01), but not with increased smoking (p = 0.60). Popular migrant adolescents were at less risk of smoking, alcohol use, and cannabis use than popular non-migrant adolescents. CONCLUSION: Homophily of social ties by migration background is noticeable in European schools. The tendency of migrant adolescents to have same-migration social ties may isolate them from non-migrant adolescents, but also reduces their risky health behaviours, in particular cannabis and alcohol use.

Using the Portuguese version of the Bicultural Scale in Brazil / O uso da versão em português da Escala de Biculturalidade no Brasil

Abstract Introduction: Brazil has received influxes of people, mainly from Africa, Europe and Japan, forming one of the most heterogeneous populations in the world. Some groups, particularly in Southern Brazil, have retained their original cultural traditions, whilst acquiring elements of the typical local Brazilian cultural identity. This is the first study designed to formally evaluate biculturality in Brazil. Objective: To psychometrically assess and validate the Portuguese version of the Bicultural Scale (BS) in Brazil. Methods: The BS was adapted and translated to Portuguese and tested for the first time in Brazil in a sample of descendants (n = 160) from four immigrant groups and respective locations in Southern Brazil. A series of psychometric tests were conducted in order to examine the validity of the Portuguese version of the BS. Analyses of variance across scores for all subgroups were also conducted. Results: Factor analysis revealed two main factors contributing to most of the variance in scores. The 10 items measuring affiliation with minority cultural characteristics and the typical Brazilian culture yielded Cronbach's alpha coefficients of 0.69 and 0.78 respectively, whereas the overall Cronbach's alpha for all 20 items of the BS was 0.67. There was a significant correlation between items related to the typical Brazilian culture and the generation since immigration of research participants (r = 0.23, p = 0.004). The mean time taken to complete the questionnaire was 7.4 minutes. Conclusion: The results indicate that the Portuguese version of the BS is a valid, reliable and easy-to-use instrument to assess biculturality experienced by descendants of immigrants in southern Brazil.

Resumo Introdução: O Brasil recebeu afluxo de imigrantes principalmente da África, Europa e Japão, formando uma das populações mais heterogêneas do mundo. Alguns grupos, particularmente no Sul do Brasil, têm mantido suas tradições culturais originais, ao mesmo tempo que adquirem elementos típicos da identidade cultural brasileira local. Este é o primeiro estudo a avaliar formalmente a biculturalidade no Brasil. Objetivo: Avaliação psicométrica e validação da versão em português da Escala de Biculturalidade (EB) no Brasil. Métodos: A EB foi adaptada e traduzida para o português e testada pela primeira vez no Brasil em uma amostra de descendentes de quatro grupos de imigrantes (n = 160) em diferentes localizações no Sul do Brasil. Uma série de testes psicométricos foram aplicados a fim de examinar a validade da versão em português da EB. Análises de variância através dos escores obtidos em cada subgrupo também foram conduzidas. Resultados: A análise fatorial revelou que dois fatores principais contribuem para a maioria da variância nos escores. Os 10 items que medem afiliação com características culturais minoritárias e cultura típica brasileira demonstraram índice de Cronbach de 0,69 e 0,78, respectivamente, enquanto que o alfa global de Cronbach para todos os 20 itens da EB foi de 0,67. Houve correlação significativa entre os itens relacionados à cultura típica brasileira e a geração dos voluntários desde o período de imigração (r = 0,23, p = 0,004). O tempo médio para completar o questionário foi de 7,4 minutos. Conclusões: Os resultados indicam que a versão em português da EB é um instrumento válido, confiável e de fácil utilização para avaliar expêriencias de biculturalidade de descendentes de imigrantes no Sul do Brasil.

Informed Choice in the German Mammography Screening Program by Education and Migrant Status: Survey among First-Time Invitees.

Breast cancer is the most prevalent cancer among women and mammography screening programs are seen as a key strategy to reduce breast cancer mortality. In Germany, women are invited to the population-based mammography screening program between ages 50 to 69. It is still discussed whether the benefits of mammography screening outweigh its harms. Therefore, the concept of informed choice comprising knowledge, attitude and intention has gained importance. The objective of this observational study was to assess the proportion of informed choices among women invited to the German mammography screening program for the first time. A representative sample of 17,349 women aged 50 years from a sub-region of North Rhine Westphalia was invited to participate in a postal survey. Turkish immigrant women were oversampled. The effects of education level and migration status on informed choice and its components were assessed. 5,847 (33.7%) women responded to the postal questionnaire of which 4,113 were used for analyses. 31.5% of the women had sufficient knowledge. The proportion of sufficient knowledge was lower among immigrants and among women with low education levels. The proportion of women making informed choices was low (27.1%), with similar associations with education level and migration status. Women of low (OR 2.75; 95% CI 2.18-3.46) and medium education level (OR 1.49; 95% CI 1.27-1.75) were more likely to make an uninformed choice than women of high education level. Turkish immigrant women had the greatest odds for making an uninformed choice (OR 5.30, 95% CI 1.92-14.66) compared to non-immigrant women. Other immigrant women only had slightly greater odds for making an uninformed choice than non-immigrant women. As immigrant populations and women with low education level have been shown to have poor knowledge, they need special attention in measures to increase knowledge and thus informed choices.

Lower Risk of Cancer in the Areas Inhabited by the German Minority in the Region of Opole, Poland.

BACKGROUND: The lower risk of cancer in the areas inhabited by the German minority in the region of Opole, Poland, at the turn of the 1980's and 1990's has been already reported. A reanalysis of the present-day data was conducted. PATIENTS AND METHODS: All the cancer cases (at all sites combined) registered within the years 2008-2012 with data collected by the Regional Cancer Registry in Opole were analyzed in this study. To estimate the risk of cancer in different spatial contexts, such as trends, clusters, and levels, modern geostatistical tools were applied. RESULTS: A statistically significant reduction of the cancer risk was reported in administrative units with ≥ 10% of the German minority. Average decreases in relative risk of 13% in men and 16% in women were estimated. The geographical patterns of the estimates are illustrated. CONCLUSIONS: The observed differences in the risk of cancer between the ethnic groups (Germans and repatriates) confirm a historical trend of the disease in the region of Opole, Poland. Some genetic, nutritional, or cultural aspects together with economic issues may play a role in the specified spatial disease patterns.

The TMEM43 Newfoundland mutation p.S358L causing ARVC-5 was imported from Europe and increases the stiffness of the cell nucleus.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare genetic condition caused predominantly by mutations within desmosomal genes. The mutation leading to ARVC-5 was recently identified on the island of Newfoundland and caused by the fully penetrant missense mutation p.S358L in TMEM43. Although TMEM43-p.S358L mutation carriers were also found in the USA, Germany, and Denmark, the genetic relationship between North American and European patients and the disease mechanism of this mutation remained to be clarified. METHODS AND RESULTS: We screened 22 unrelated ARVC patients without mutations in desmosomal genes and identified the TMEM43-p.S358L mutation in a German ARVC family. We excluded TMEM43-p.S358L in 22 unrelated patients with dilated cardiomyopathy. The German family shares a common haplotype with those from Newfoundland, USA, and Denmark, suggesting that the mutation originated from a common founder. Examination of 40 control chromosomes revealed an estimated age of 1300-1500 years for the mutation, which proves the European origin of the Newfoundland mutation. Skin fibroblasts from a female and two male mutation carriers were analysed in cell culture using atomic force microscopy and revealed that the cell nuclei exhibit an increased stiffness compared with TMEM43 wild-type controls. CONCLUSION: The German family is not affected by a de novo TMEM43 mutation. It is therefore expected that an unknown number of European families may be affected by the TMEM43-p.S358L founder mutation. Due to its deleterious clinical phenotype, this mutation should be checked in any case of ARVC-related genotyping. It appears that the increased stiffness of the cell nucleus might be related to the massive loss of cardiomyocytes, which is typically found in ventricles of ARVC hearts.

[Muscular sarcocystosis after travel to Malaysia: a case series from Germany]. / Muskuläre Sarkozystose nach Malaysiareise: eine Fallserie aus Deutschland.

BACKGROUND: Since 2011, about 100 travellers to the island of Tioman, Malaysia, have been diagnosed worldwide with suspected muscular sarcocystosis, a previously only sporadically observed parasitic disease. Source of infection and therapy remain unclear. Final diagnosis requires microscopic identification of cysts in muscle biopsies. The study objective was a systematic description of characteristic symptoms, laboratory investigations and treatment response. METHODS: Systematic case series. RESULTS: The 26 cases of 5 centers for tropical medicine in Germany showed a characteristic biphasic development: symptoms began in general 2 weeks after mid-holidays (min. 7.5, max. 22 days) with unspecific fever and headaches lasting for almost 1 week. After an asymptomatic period of 2 weeks, severe myalgia (6.5, scale 0-10) and fever developed and lasted for about 6 weeks (min. 7, max. 207 days), accompanied by creatin-phosphokinase(CK)-elevation (up to 3.5 times), and eosinophilia (2.9 times). One out of two muscle biopsies revealed a cyst typical for sarcocystosis. In 6 out of 7 patients an increase in Sarcocystis-specific antibody concentration could be demonstrated by ELISA. Treatment with systemic steroids and albendazole, or ivermectin resulted in significant symptomatic improvement in most of the patients. One patient was treated early with cotrimoxazole and subsequently did not develop a second phase of the disease. All patients had stayed in the North-West of the island Tioman. CONCLUSIONS: Muscular sarcocystosis develops in a biphasic pattern with initial fever and later prolonged myalgia, eosinophilia, and CK-elevation. Steroids achieve symptomatic relief in the late phase. Early cotrimoxazole-therapy could possibly prevent parasitic muscle invasion. In fever after travel to Malaysia differential diagnosis should include sarcocystosis. The source of infection appears to be located in North-West of Tioman. Further studies are needed, including addressing early diagnosis and treatment.

Alemanha e Brasil, 1870-1945: uma relação entre espaços / Germany and Brazil, 1870-1945: a relationship between spaces

As relações entre Alemanha e Brasil foram influenciadas por diferentes ordens espaciais que coexistiram e se influenciaram, no período de 1870 a 1945. O artigo discute a ideia de viver em mundos diferentes, muito distantes entre si. Argumenta-se que o conceito de distância mudou lenta e regularmente com o aparecimento de modernas tecnologias de comunicação. Ordens espaciais hierarquicamente estruturadas em centros e periferias dominaram as relações nesse período. Os alemães consideravam seu espaço maior e superior ao brasileiro, situação com a qual muitos brasileiros, naquela época, concordavam, entretanto, desde a Primeira Guerra Mundial, não mais quiseram aceitar essa suposta ordem natural.

Relations between Germany and Brazil were influenced by different spatial orders which co-existed and influenced each other between 1870 and 1945. The article discusses the idea of living in different worlds, and being worlds apart. It argues that the concept of distance changed slowly, but surely, with the rise of modern communication technologies. Hierarchically structured spatial orders of centers and peripheries dominated the relationship in this period. Not only the Germans considered their own space superior, and on a higher level than the Brazilian, many Brazilians of the time agreed with this point of view, but also, since the First World War, were not willing to accept this allegedly natural order of the globe any longer.

Colorectal cancer stage at diagnosis in migrants versus non-migrants (KoMigra): study protocol of a cross-sectional study in Germany.

BACKGROUND: In Germany, about 20% of the total population have a migration background. Differences exist between migrants and non-migrants in terms of health care access and utilisation. Colorectal cancer is the second most common malignant tumour in Germany, and incidence, staging and survival chances depend, amongst other things, on ethnicity and lifestyle. The current study investigates whether stage at diagnosis differs between migrants and non-migrants with colorectal cancer in an area of high migration and attempts to identify factors that can explain any differences. METHODS/DESIGN: Data on tumour and migration status will be collected for 1,200 consecutive patients that have received a new, histologically verified diagnosis of colorectal cancer in a high migration area in Germany in the previous three months. The recruitment process is expected to take 16 months and will include gastroenterological private practices and certified centres for intestinal diseases. Descriptive and analytical analysis will be performed: the distribution of variables for migrants versus non-migrants and participants versus non-participants will be analysed using appropriate χ2-, t-, F- or Wilcoxon tests. Multivariable, logistic regression models will be performed, with the dependent variable being the dichotomized stage of the tumour (UICC stage I versus more advanced than UICC stage I). Odds ratios and associated 95%-confidence intervals will be calculated. Furthermore, ordered logistic regression models will be estimated, with the exact stage of the tumour at diagnosis as the dependent variable. Predictors used in the ordered logistic regression will be patient characteristics that are specific to migrants as well as patient characteristics that are not. Interaction models will be estimated in order to investigate whether the effects of patient characteristics on stage of tumour at the time of the initial diagnosis is different in migrants, compared to non-migrants. DISCUSSION: An association of migration status or other socioeconomic variables with stage at diagnosis of colorectal cancer would be an important finding with respect to equal health care access among migrants. It would point to access barriers or different symptom appraisal and, in the long term, could contribute to the development of new health care concepts for migrants. TRIAL REGISTRATION: German Clinical Trials Register DRKS00005056.

TAS2R38 and its influence on smoking behavior and glucose homeostasis in the German Sorbs.

BACKGROUND: Genetic variants within the bitter taste receptor gene TAS2R38 are associated with sensitivity to bitter taste and are related to eating behavior in the Amish population. Sensitivity to bitter taste is further related to anthropometric traits in an genetically isolated Italian population. We tested whether the TAS2R38 variants (rs713598; rs1726866 and rs10246939) may be related to eating behavior, anthropometric parameters, metabolic traits and consumer goods intake in the German Sorbs. MATERIALS AND METHODS: The three SNPs were genotyped in a total cohort of 1007 individuals (male/female: 405/602). The German version of the three-factor eating questionnaire was completed by 548 individuals. Genetic association analyses for smoking behavior, alcohol and coffee intake, eating behavior factors (restraint, disinhibition and hunger) and other metabolic traits were analyzed. Further, by combining the three SNPs we applied comparative haplotype analyses categorizing PAV (proline-alanine-valine) carriers (tasters) vs. homozygous AVI (alanin-valine-isoleucine) carriers (non-tasters). RESULTS: Significant associations of genetic variants within TAS2R38 were identified with percentage of body fat, which were driven by associations in women. In men, we observed significant associations with 30 min plasma glucose, and area under the curve for plasma glucose (0-120 min) (all adjusted P≤0.05). Further, we found that carriers of at least one PAV allele show significantly lower cigarette smoking per day (P = 0.002) as well as, albeit non-significant, lower alcohol intake. We did not confirm previously reported associations between genetic variants of TAS2R38 and eating behavior. CONCLUSION: Our data suggest that genetic variation in TAS2R38 is related to individual body composition measures and may further influence consumer goods intake in the Sorbs possibly via individual sensitivity to bitter taste.

THOC5: a novel gene involved in HDL-cholesterol metabolism.

Although numerous genes are known to regulate serum lipid traits, identified variants explain only a small proportion of the expected heritability. We intended to identify further genetic variants associated with lipid phenotypes in a self-contained population of Sorbs in Germany. We performed a genome-wide association study (GWAS) on LDL-cholesterol, HDL-cholesterol (HDL-C), and triglyceride (TG) levels in 839 Sorbs. All single-nucleotide polymorphisms with a P value <0.01 were subjected to a meta-analysis, including an independent Swedish cohort (Diabetes Genetics Initiative; n = ∼3,100). Novel association signals with the strongest effects were subjected to replication studies in an additional German cohort (Berlin, n = 2,031). In the initial GWAS in the Sorbs, we identified 14 loci associated with lipid phenotypes reaching P values <10⁻5 and confirmed significant effects for 18 previously reported loci. The combined meta-analysis of the three study cohorts (n(HDL) = 6041; n(LDL) = 5,995; n(TG) = 6,087) revealed a novel association for a variant in THOC5 (rs8135828) with serum HDL-C levels (P = 1.78 × 10⁻7; Z-score = -5.221). Consistently, the variant was also associated with circulating APOA1 levels in Sorbs. The small interfering RNA-mediated mRNA silencing of THOC5 in HepG2 cells resulted in lower mRNA levels of APOA1, SCARB1, and ABCG8 (all P < 0.05). We propose THOC5 to be a novel gene involved in the regulation of serum HDL-C levels.

Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity.

In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case-control study of 1,089 oldest-old (ages 92-93) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-110) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R (2)=0.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11 years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected=0.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N=563) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.