Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldWe recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism

Optimizing diagnostic tests for persulphate:induced respiratory diseases

BACKGROUND: Persulphates from hair bleaching products are considered the major cause of occupational-rhinitis and asthma in hairdressers. The specific inhalation challenge (SIC) is considered ‘reference standard’ for diagnosing persulphate-induced asthma and rhinitis; however, the currently validated method of performing SIC with persulphate powder is time consuming with a duration of up to 4 days. The value of skin prick tests (SPTs) and histamine release tests (HRTs) with persulphates is unknown. The aim of this study was to establish a novel rapid SIC with persulphate powder to test for both rhinitis and asthma simultaneously in 1 day. In addition, we assessed the suitability of SPTs and HRTs for detecting persulphate-induced respiratory diseases. METHODS: The study population included 19 hairdressers with a history of work-related rhinitis and/or asthma symptoms, 12 symptomatic controls (10 with concurrent allergic asthma and rhinitis and two with non-allergic asthma), and 40 healthy controls. A previous severe asthmatic reaction and/or anaphylactic reaction to persulphates was considered an exclusion criterion for hairdressers. The 19 hairdressers and 12 symptomatic controls had SIC performed with 3 × 5 min exposures to potassium persulphate powder in a provocation chamber. All participants, including the 40 healthy controls, were subjected also to SPTs and HRTs with three persulphate salts at concentrations of 2–20 % and 0.03–1 %, respectively. RESULTS: None of the symptomatic controls had a nasal or bronchial response to SIC with potassium persulphate. Six hairdressers presented a nasal and two a bronchial response. No severe reactions occurred. No positive SPTs were recorded, neither among hairdressers, symptomatic controls, nor healthy controls. All three groups showed nonspecific non-IgE mediated histamine release to persulphates in HRT. CONCLUSIONS: The proposed method for performing SIC showed a high specificity for detecting persulphate-induced asthma and rhinitis. The rapid SIC was able to produce positive nasal and bronchial responses in symptomatic hairdressers without any severe reactions occurring. SPTs and HRTs cannot predict asthma or rhinitis caused by persulphates

Clinical response and remission in severe asthma patients treated with biologic therapies

BACKGROUND: The development of novel targeted biologic therapies for severe asthma has provided an opportunity to consider remission as a new treatment goal.RESEARCH QUESTION: How many severe asthma patients treated with biologic therapy achieve clinical remission, and what predicts response to treatment?STUDY DESIGN AND METHODS: The Danish Severe Asthma Registry is a nationwide register including all adult patients receiving biologic therapy for severe asthma in Denmark. We conducted an observational cohort study and defined "clinical response" to treatment after 12 months as ≥50% reduction in exacerbations, and/or a ≥50% reduction in maintenance oral corticosteroid dose, if required. "Clinical remission" was defined by cessation of exacerbations and maintenance OCS, as well as a normalization of lung function (FEV1%&gt;80%) and an Asthma Control Questionnaire-6 score ≤1.50 after 12 months of treatment.RESULTS: After 12 months of treatment of 501 biologically naïve patients, there were 104 (21%) patients with no response to treatment, whereas 397 (79%) had a clinical response. Among the latter, 97 (24%) fulfilled our criteria of clinical remission, corresponding to 19% in the entire population. Remission was predicted by shorter duration of disease and lower BMI in our entire population of all patients treated with biologic therapy.INTERPRETATION: Clinical response was achieved in most adult patients initiating biologic therapy and clinical remission was observed in 19% of the patients after 12 months of treatment. Further studies are required to assess the long-term outcome of achieving clinical remission on biologic therapy.</p

Attitudes towards sickness absence and sickness presenteeism in health and care sectors in Norway and Denmark: a qualitative study

BACKGROUND: In the health and care sector, sickness absence and sickness presenteeism are frequent phenomena and constitute a field in need of exploration. Attitudes towards sickness absence involve also attitudes towards sickness presenteeism, i.e. going to work while sick, confirmed by previous studies. Sickness behavior, reflecting attitudes on work absence, could differ between countries and influence absence rates. But little is known about attitudes towards sickness absence and sickness presenteeism in the health and care sectors in Norway and Denmark. The aim of the present paper is therefore to explore attitudes towards sickness absence and sickness presenteeism among nursing home employees in both countries. METHODS: Eight focus group discussions (FGDs) were conducted using a semi-structured interview guide, the main attention of which was attitudes towards sickness absence and sickness presenteeism. FGDs were conducted in two nursing homes in Norway and two in Denmark, with different geographic locations: one in a rural area and one in an urban area in each country. FGDs were recorded, transcribed and analyzed using framework analysis to identify major themes and explanatory patterns. RESULTS: Four major significant themes were identified from the FGDs: a) sickness absence and sickness presenteeism, b) acceptable causes of sickness absence, c) job identity, and d) organization of work and physical aspects of the workplace. Our analyses showed that social commitment and loyalty to residents and colleagues was important for sickness absence and sickness presenteeism, as were perceived acceptable and non-acceptable reasons for sickness absence. Organization of work and physical aspects of the workplace were also found to have an influence on attitudes towards sickness absence. CONCLUSIONS: The general interpretation of the findings was that attitudes towards sickness absence and sickness presenteeism among nursing home employees were embedded in situational patterns of moral relationships and were connected to a specific job identity. These patterns were constituted by the perception of colleagues, the social commitment to residents, and they influence on what was deemed as acceptable and non-acceptable reasons for sickness absence. In other words, attitudes towards sickness absence and sickness presenteeism were socially and morally determined at personal levels by an overall concept of work, independent of country

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.

To access publisher full text version of this article. Please click on the hyperlink in Additional LinkWe conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion