Anaque Oliveira Pires

Polymorphisms in the DAD1 and OXA1L genes are associated with asthma and atopy in a South American population

HighlightsGenetic variants in the DAD1 and OXA1L genes are significantly associated with asthma and/or allergy markers.We have demonstrated increased DAD1 expression levels in asthmatic individuals.These variants are involved in regulatory mechanisms and may impact the occurrence of asthma and allergy in our population. &NA; Atopic asthma, which is characterized by the chronic inflammation and morbidity of airways, is a disease of great complexity, and multiple genetic and environmental factors are involved in its etiology. In the first genome‐wide association study (GWAS) conducted in Brazil for asthma, a positive association was found between atopic asthma and a variant (rs1999071), which is located between the DAD1 and OXA1L genes, although neither gene has previously been reported to be associated with asthma or allergies. The DAD1 gene is involved in the regulation of programmed cell death, and OXA1L is involved in biogenesis and mitochondrial oxidative phosphorylation. This study aimed to evaluate how polymorphisms in DAD1 and OXA1L are associated with asthma and markers of atopy in individuals from the Salvador cohort of the SCAALA (Social Change Asthma and Allergy in Latin America) program. The DNA of 1220 individuals was genotyped using the Illumina 2.5 Human Omni Bead chip. Logistic regression analyses were performed with PLINK 1.9 software to verify the association between DAD1 and OXA1L polymorphisms and asthma and atopic markers, adjusted for sex, age, helminth infections and ancestry markers, using an additive model. The DAD1 and OXA1L genes were associated with some of the evaluated phenotypes, such as asthma, skin prick test (SPT), specific IgE for aeroallergens, and Th1/Th2‐type cytokine production. Using qPCR, as well as in silico gene expression analysis, we have demonstrated that some of the polymorphisms in both genes are able to affect their respective gene expression levels. In addition, DAD1 was over‐expressed in asthmatic patients when compared with controls. Thus, our findings demonstrate that variants in both the DAD1 and OXA1L genes may affect atopy and asthma in a Latin American population with a high prevalence of asthma.

Effects of Anonna muricata L. (soursop) seeds oil improves in model in vivo and in vitro of type 1 diabetes mellitus

S A T U R D Juliana Durack, Nikole E. Kimes, Din Lin, Michelle McKean, Marcus Rauch, Michael D. Cabana, and S. V. Lynch; University of California, San Francisco, CA, University of California San Francisco, San Francisco, CA. RATIONALE: Neonatal gut microbiome perturbation is associated with childhood allergic asthma development. Daily Lactobacillus rhamnosus GG supplementation of high-risk (HR) for asthma infants from birth may impact the compositional and functional development of the gut microbiome in a manner that promotes immune tolerance. METHODS: Longitudinal stool samples from 25 HR infants (randomized to receive 1x10 LGG or placebo daily, from birth to 6mo), and 29 healthy control (HC) infants were subjected to 16S rRNA-based microbiota and un-targeted liquid chromatography mass spectrometry metabolomic profiling. A dendritic-cell/T-cell co-culture assaywas used to assess the capacity of sterile fecal water from a subset of 6mo and 12mo samples to promote T-regulatory cell populations and IL10 production. RESULTS: Compared to healthy controls, placebo-treated HR subjects exhibited delayed bacterial diversification over the first year of life, which was abrogated in LGG supplemented subjects. Compared to the placebo arm, LGG supplementation was associated with gut bacterial communities and fecal metabolic profiles more similar to healthy control subjects. At 6 months LGG-supplemented subjects exhibited enrichment of a range of anti-inflammatory metabolites, and sterile fecal water prepared from these participants promoted expansion of CD4+CD25+Foxp3+ (T-regulatory) cells and IL10 ex vivo. These effects were lost at 12 months, 6 months following cessation of LGG supplementation. CONCLUSIONS: Daily LGG supplementation in early life partially rescues gut microbiome and metabolome deficiencies associated with high-risk for asthma subjects. Sustained supplementation or supplementation with a cocktail of bacteria typically depleted in HR infants may be necessary to prevent allergic asthma in childhood.