A Review of the Impact of Occupational Contact Dermatitis on Quality of Life

Occupational contact dermatitis (OCD) is the most common occupational skin disease in many countries. We reviewed the current evidence on how OCD impacts on quality of life (QoL). The three commonly used QoL questionnaires in OCD were the Short-Form Health Survey (SF-36), the Dermatology Life Quality Index (DLQI), and the Skindex. Despite the availability of a variety of validated QoL instruments, none of them is specific to OCD or entirely adequate in capturing the impact of OCD on QoL. Nonetheless, the results of this paper do suggest a significant impact. Use of QoL measures in clinical settings will provide patients with an opportunity to express their concerns and assist clinicians to evaluate the effectiveness of management beyond the clinical outcomes. This paper also highlights the lack of a disease-specific QOL instrument and the importance of developing a validated measure to assess QOL in OCD, enabling comparison across countries and occupational groups

自己中心座標に基づく観光用ナビゲーション

電気通信大学201

Gene-based analysis of regulatory variants identifies 4 putative novel asthma risk genes related to nucleotide synthesis and signaling

Background Hundreds of genetic variants are thought to contribute to variation in asthma risk by modulating gene expression. Methods that increase the power of genome-wide association studies (GWASs) to identify risk-associated variants are needed. Objective We sought to develop a method that aggregates the evidence for association with disease risk across expression quantitative trait loci (eQTLs) of a gene and use this approach to identify asthma risk genes. Methods We developed a gene-based test and software package called EUGENE that (1) is applicable to GWAS summary statistics; (2) considers both cis- and trans-eQTLs; (3) incorporates eQTLs identified in different tissues; and (4) uses simulations to account for multiple testing. We applied this approach to 2 published asthma GWASs (combined n\ua0=\ua046,044) and used mouse studies to provide initial functional insights into 2 genes with novel genetic associations. Results We tested the association between asthma and 17,190 genes that were found to have cis- and/or trans-eQTLs across 16 published eQTL studies. At an empirical FDR of 5%, 48 genes were associated with asthma risk. Of these, for 37, the association was driven by eQTLs located in established risk loci for allergic disease, including 6 genes not previously implicated in disease cause (eg, LIMS1, TINF2, and SAFB). The remaining 11 significant genes represent potential novel genetic associations with asthma. The association with 4 of these replicated in an independent GWAS: B4GALT3, USMG5, P2RY13, and P2RY14, which are genes involved in nucleotide synthesis or nucleotide-dependent cell activation. In mouse studies, P2ry13 and P2ry14—purinergic receptors activated by adenosine 5-diphosphate and UDP-sugars, respectively—were upregulated after allergen challenge, notably in airway epithelial cells, eosinophils, and neutrophils. Intranasal exposure with receptor agonists induced the release of IL-33 and subsequent eosinophil infiltration into the lungs. Conclusion We identified novel associations between asthma and eQTLs for 4 genes related to nucleotide synthesis/signaling and demonstrated the power of gene-based analyses of GWASs

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis

Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology

Asthma, hay fever (or allergic rhinitis) and eczema (or atopic dermatitis) often coexist in the same individuals, partly because of a shared genetic origin. To identify shared risk variants, we performed a genome-wide association study (GWAS; n = 360,838) of a broad allergic disease phenotype that considers the presence of any one of these three diseases. We identified 136 independent risk variants (P < 3 × 10-8), including 73 not previously reported, which implicate 132 nearby genes in allergic disease pathophysiology. Disease-specific effects were detected for only six variants, confirming that most represent shared risk factors. Tissue-specific heritability and biological process enrichment analyses suggest that shared risk variants influence lymphocyte-mediated immunity. Six target genes provide an opportunity for drug repositioning, while for 36 genes CpG methylation was found to influence transcription independently of genetic effects. Asthma, hay fever and eczema partly coexist because they share many genetic risk variants that dysregulate the expression of immune-related genes

Associations between reduced diffusing capacity and airflow obstruction in community-based subjects

Introduction: The purpose of this analysis was to determine if abnormal diffusing capacity of the lung for carbon monoxide (DLco) identified a group of subjects with significantly different characteristics than those with normal lung function or airflow obstruction alone. Methods: Participants were a random sample of adults aged 45–70 years. They completed a detailed respiratory questionnaire, spirometry, methacholine challenge and measurement of single breath DLco. Subjects were categorized into one of three groups: airflow obstruction only, reduced DLco only, or both airflow obstruction and reduced DLco. Results: Individuals with airflow obstruction and reduced DLco in combination reported more symptoms than those with either condition alone. In subjects with a combination of both airflow obstruction and reduced DLco, a significantly higher proportion reported use of medication and laboratory tests. Current smoking was significantly associated with a reduced DLco alone and in combination with airflow obstruction, however, the association was stronger in those with DLco and airflow obstruction. Bronchial hyperreactivity (BHR) was found to be a risk factor while atopy was associated with a reduced risk of DLco and airflow obstruction. Conclusions: Reduced DLco plus airflow obstruction together identifies a group of individuals with significantly more symptoms and worse lung function. Current cigarette smoking, early life serious respiratory infection and BHR were strongly associated with reduced DLco in combination with airflow obstruction

Microsomal epoxide hydrolase is not associated with COPD in a community-based sample

Microsomal epoxide hydrolase (EPHX1) is an important gene because of its role in the metabolism of components of cigarette smoke; thus it may be an important potential modifier of the risk of developing smoking-related lung disease, such as chronic obstructive pulmonary disease (COPD). Several studies have investigated EPHX1 and COPD, but some of these studies have potentially been affected by genotyping error. We investigated the influence of single nucleotide polymorphisms (SNPs) in EPHX1 on well-characterized COPD and intermediate phenotypes. A total of 1,232 participants completed a detailed respiratory questionnaire and spirometry. From this sample, 72 COPD cases (FEV1/FVC \u3c 0.70 and FEV1 \u3c 80% predicted) and 220 control subjects (no respiratory symptoms and normal lung function) were selected for analysis. The EPHX1 exon 3 and EPHX1 exon 4 polymorphisms were carefully genotyped to avoid error using several methods. We found that the EPHX1 exon 3 polymorphism was not associated with an increased risk of COPD, nor was the EPHX1 exon 4 polymorphism. In addition, none of the EPHX1 haplotypes were associated with an increased risk of any COPD phenotype. This finding, along with doubt shed on the accuracy of other studies that have demonstrated positive associations, suggests that a strong role for the EPHX1 polymorphisms in respiratory disease is unlikely

Association of IL8, CXCR2 and TNF-α polymorphisms and airway disease

Chronic obstructive pulmonary disease (COPD) is a disease characterised by inflammation of the peripheral airways involving many inflammatory cells and mediators. IL8 is an important inflammatory mediator that is responsible for the migration and activation of neutrophils. Cellular activity of IL8 is mediated by the receptor CXCR2, and transcription of IL8 is controlled by the cytokine tumour necrosis factor (TNFα). The aim of our study was to investigate the influence of single nucleotide polymorphisms in IL8, CXCR2 and TNF-α on lung function and respiratory symptoms in subjects from Melbourne, Australia. A total of 1,232 participants completed a detailed respiratory questionnaire, spirometry and measurement of gas transfer. Genotyping for the IL8 -251 T→A, CXCR2 +785C→T and TNF-α -308G→A polymorphisms was performed using the tetra-primer ARMS-PCR method. The TNF-α A allele was associated with a reduced FEF25–75 ( P=0.03). Inheritance of the CXCR2 T allele was associated with significantly higher diffusing capacity ( P=0.03) and FEF25–75 ( P=0.02). No association with the IL8 -251 polymorphism was found. Our results suggest that TNF-α is associated with COPD-related phenotypes and the CXCR2 +785 SNP may be important in protecting against pulmonary inflammation. These genes may be important candidates in the modulation of the inflammatory response in the airways