Human leucocyte antigens (HLA) and trimellitic anhydride (TMA) immunological lung disease

AbstractOccupational immunological lung disease, due to low molecular weight, reactive chemicals such as trimellitic anhydride (TMA), is an emerging health problem. If there were a marker that was highly predictive of the ability of the immune system to recognize TMA as an allergen, better prevention strategies could be employed with at risk individuals. The purpose of this study is to evaluate whether human leucocyte antigen (HLA) class specificity is associated with the development of late respiratory systemic syndrome (LRSS) or asthma due to immunological sensitivity to trimellitic anhydride (TMA). This is a case control study of 17 individuals with LRSS, 12 with asthma and 22 TMA similarly exposed individuals who did not develop LRSS or asthma. Comparing the sensitized individuals (LRSS or asthma) with the non-sensitized individuals (controls), we found no difference in frequency of any HLA antigen. In summary, the lack of association of HLA antigens with LRSS or asthma due to TMA suggests that these will not be useful markers to identify at risk individuals

Differential enzymatic activity of common haplotypic versions of the human acidic Mammalian chitinase protein

FWN – Publicaties zonder aanstelling Universiteit Leide

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 50y, women 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.Peer reviewe

Occupational asthma and extrinsic alveolitis due to isocyanates: current status and perspectives.

Isocyanates are used for the large scale production of polyurethane polymers, which have an almost endless variety of applications in the manufacture of flexible and rigid foams, elastomers, adhesives, and surface coatings. Acute or chronic exposure to high concentrations of isocyanates can result in respiratory health hazards through a direct irritant effect. Isocyanates are of special interest, however, because, in some exposed workers, they can cause occupational asthma or extrinsic alveolitis through an apparently sensitising mechanism.Because of their wide industrial use, isocyanates are the principal cause of occupational asthma which is now the most common respiratory disease linked to the working environment. This review focuses on recently studied aspects of occupational asthma and extrinsic alveolitis related to exposure to isocyanates