Susceptibility to asthma and eczema from mucosal and epidermal expression of distinctive genes

The past several years have seen an increase in the rate at which genes that are associated with allergic asthma and eczema are discovered. This review examines genetic association, gene expression, and functional studies that have identified genes that are expressed in the epithelial cells of the skin and lung and are involved in the pathogenesis of allergic asthma and eczema. This includes the genes encoding thymic stromal lymphopoietin (TSLP) and suppressor of cytokine signalling (SOCS3) that are involved in the activation of T-helper 2 cells, the microbial pattern recognition receptors nucleotide-binding oligomerization domain (NOD) genes (CARD4 and CARD15), Toll-like receptors (TLR2 and TLR4), and filaggrin, a protein required for effective barrier defense of the skin. Therefore, the development of allergic disease involves both the adaptive and innate immune systems, and the expression of these genes in the skin and lungs suggests a link to environmental triggers at body surfaces

Telomere length in early childhood : early life risk factors and association with carotid intima-media thickness in later childhood

Background Reduced telomere length is a measure of biological aging that is predictive of cardiac events in adults, and has been mechanistically implicated in the onset and progression of atherosclerosis. We sought to describe the early life factors associated with leukocyte telomere length in early childhood, and to determine whether telomere length measured during early childhood is associated with arterial wall thickening later in childhood. Design A longitudinal birth cohort recruited antenatally in Sydney from 1997 to 1999. Methods Leukocyte telomere length was measured in 331 children at age 3.6 years (SD 1.0); of whom 268 children without diabetes had carotid intima-media thickness assessed by ultrasound at age 8 years. Results Male sex, younger paternal age and higher maternal body mass index were associated with shorter telomere length in early childhood, which in turn was associated with greater carotid intima-media thickness at age 8 years (standardised β = -0.159, P = 0.01). There was a graded association across quartiles of telomere length (Ptrend = 0.001) with the highest odds of elevated intima-media thickness (˃75th percentile) being in children with the shortest telomeres (odds ratio 4.00 (95% confidence interval 1.58 to 10.14) relative to those with the longest telomeres, P = 0.003). This association remained after adjustment for early life risk factors (Ptrend = 0.001). Conclusions Reduced telomere length in early childhood is independently associated with arterial wall thickness in later childhood, suggesting that reduced telomere length during early childhood may be a marker of vascular disease risk

The 10q25.3-26.1 G protein-coupled receptor gene GPR26 is epigenetically silenced in human gliomas

Loss of heterozygosity (LOH) of the entire chromosome 10 is the most frequent genetic alteration in human glioblastoma (GBM). In addition to PTEN/MMAC1 on 10q23.3, clustering of partial deletion break-points on 10q25.3-26.1 points to a second suppressor locus. The proposed target gene DMBT1 was not confirmed. By somatic deletion mapping of this region, we identified the complementary DNA encoding the human homologue of rat orphan G protein-coupled receptor GPR26. GPR26 is highly expressed in fetal and adult brain, but frequently reduced or absent in glioma cells and biopsies, due to de novo methylation of its 5' CpG island. Silencing of GPR26 was reversed with 5-aza-deoxycytidine and the histone deacetylase inhibitor trichostatin A. Furthermore, overexpression of GPR26 in HEK and in U87 glioma cells increased intracellular cAMP concentration which is considered to induce astrocytic differentiation. Interestingly, we observed concomitant silencing of GPR26 with O6-methylguanine-DNA methyl transferase (MGMT), a DNA repair gene co-localized on 10q25.3-26.1 (p=0.0001). We conclude that epigenetic silencing is a common mechanism in malignant gliomas that simultaneously inactivates MGMT and GPR26. The 10q25.3-26.1 region may contain an important epigenetic pathway in brain tumorigenesis

Cohort profile : the Childhood Asthma Prevention Study (CAPS)

The Childhood Asthma Prevention Study (CAPS) commenced in 1997 in Sydney, Australia, because of concern about the high and increasing prevalence of childhood asthma. Cross-sectional and ecological studies had shown that exposure to high concentrations of house dust mite (HDM) allergen and being sensitized to HDM were both associated with increased prevalence. Other studies had indicated that children who regularly consumed oily fish containing high levels of omega-3 fatty acids were less likely to have airway hyper-responsiveness (AHR) and asthma. Those who regularly consumed oils and spreads containing polyunsaturated fats with a higher proportion of omega-6 fatty acids had an increased prevalence of asthma-like symptoms