A foundation for provitamin A biofortification of maize: genome-wide association and genomic prediction models of carotenoid levels.

Efforts are underway for development of crops with improved levels of provitamin A carotenoids to help combat dietary vitamin A deficiency. As a global staple crop with considerable variation in kernel carotenoid composition, maize (Zea mays L.) could have a widespread impact. We performed a genome-wide association study (GWAS) of quantified seed carotenoids across a panel of maize inbreds ranging from light yellow to dark orange in grain color to identify some of the key genes controlling maize grain carotenoid composition. Significant associations at the genome-wide level were detected within the coding regions of zep1 and lut1, carotenoid biosynthetic genes not previously shown to impact grain carotenoid composition in association studies, as well as within previously associated lcyE and crtRB1 genes. We leveraged existing biochemical and genomic information to identify 58 a priori candidate genes relevant to the biosynthesis and retention of carotenoids in maize to test in a pathway-level analysis. This revealed dxs2 and lut5, genes not previously associated with kernel carotenoids. In genomic prediction models, use of markers that targeted a small set of quantitative trait loci associated with carotenoid levels in prior linkage studies were as effective as genome-wide markers for predicting carotenoid traits. Based on GWAS, pathway-level analysis, and genomic prediction studies, we outline a flexible strategy involving use of a small number of genes that can be selected for rapid conversion of elite white grain germplasm, with minimal amounts of carotenoids, to orange grain versions containing high levels of provitamin A

Level of education and asthma control in adult-onset asthma

Objective Education in itself and as a proxy for socioeconomic status, may influence asthma control, but remains poorly studied in adult-onset asthma. Our aim was to study the association between the level of education and asthma control in adult-onset asthma. Methods Subjects with current asthma with onset >15 years were examined within the Obstructive Lung Disease in Northern Sweden study (OLIN, n = 593), Seinajoki Adult Asthma Study (SAAS, n = 200), and West Sweden Asthma Study (WSAS, n = 301) in 2009-2014 in a cross-sectional setting. Educational level was classified as primary, secondary and tertiary. Uncontrolled asthma was defined as Asthma Control Test (ACT) score Results In each cohort and in pooled data of all cohorts, median ACT score was lower among those with primary education than in those with secondary and tertiary education. Uncontrolled asthma was most common among those with primary education, especially among daily ICS users (42.6% primary, 28.6% secondary and 24.2% tertiary; p = 0.001). In adjusted analysis, primary education was associated with uncontrolled asthma in daily ICS users (OR 1.92, 95% CI 1.15-3.20). When stratified by atopy, the association between primary education and uncontrolled asthma was seen in non-atopic (OR 3.42, 95% CI 1.30-8.96) but not in atopic subjects. Conclusions In high-income Nordic countries, lower educational level was a risk factor for uncontrolled asthma in subjects with adult-onset asthma. Educational level should be considered in the management of adult-onset asthma.Peer reviewe

Expansion of CD4+CD25+ helper T cells without regulatory function in smoking and COPD

<p>Abstract</p> <p>Background</p> <p>Regulatory T cells have been implicated in the pathogenesis of COPD by the increased expression of CD25 on helper T cells along with enhanced intracellular expression of FoxP3 and low/absent CD127 expression on the cell surface.</p> <p>Method</p> <p>Regulatory T cells were investigated in BALF from nine COPD subjects and compared to fourteen smokers with normal lung function and nine never-smokers.</p> <p>Results</p> <p>In smokers with normal lung function, the expression of CD25⁺CD4⁺was increased, whereas the proportions of FoxP3⁺and CD127⁺were unchanged compared to never-smokers. Among CD4⁺cells expressing high levels of CD25, the proportion of FoxP3⁺cells was decreased and the percentage of CD127⁺was increased in smokers with normal lung function. CD4⁺CD25⁺cells with low/absent CD127 expression were increased in smokers with normal lung function, but not in COPD, when compared to never smokers.</p> <p>Conclusion</p> <p>The reduction of FoxP3 expression in BALF from smokers with normal lung function indicates that the increase in CD25 expression is not associated with the expansion of regulatory T cells. Instead, the high CD127 and low FoxP3 expressions implicate a predominantly non-regulatory CD25⁺helper T-cell population in smokers and stable COPD. Therefore, we suggest a smoking-induced expansion of predominantly activated airway helper T cells that seem to persist after COPD development.</p

Allergic rhinitis in northern vietnam: increased risk of urban living according to a large population survey

<p>Abstract</p> <p>Background</p> <p>Little is known about prevalence and risk factors of allergic rhinitis and chronic nasal symptoms among adults in Vietnam. We aimed to estimate the prevalence, risk factor patterns and co-morbidities of allergic rhinitis and chronic nasal symptoms in one urban and one rural area in northern Vietnam.</p> <p>Methods</p> <p>A cross-sectional questionnaire survey was conducted from August 2007 to January 2008 in urban Hoankiem and rural Bavi in Hanoi among adults aged 21-70 years. Of 7008 randomly selected subjects, 91.7% participated in Bavi and 70.3% in Hoankiem.</p> <p>Results</p> <p>Allergic rhinitis ever or chronic nasal symptoms were reported by 50.2%. The prevalence of allergic rhinitis ever was considerably higher in Hoankiem compared to Bavi, 29.6% vs 10.0% (p < 0.001). Allergic rhinitis ever and chronic nasal symptoms were both significantly associated with asthma and respiratory symptoms, respectively (p < 0.001). Exposure to gas, dust or fumes at work was significantly associated with allergic rhinitis ever, OR 1.57 (95% CI 1.34 - 1.84), nasal blocking, OR 1.90 (95% CI 1.68 - 2.15) and runny nose, OR 1.32 (95% CI 1.17 - 1.49), while somewhat surprisingly no association with smoking was found. Female sex was a significant risk factor for both nasal blocking and runny nose.</p> <p>Conclusions</p> <p>Allergic rhinitis ever was considerably more common in the urban area. Nasal blocking and runny nose was each reported by about one third of the studied sample with no major urban-rural difference. Further, exposure to air pollution at work was significantly associated with allergic rhinitis ever, nasal blocking and runny nose.</p

Cigarette smoking, cadmium exposure, and zinc intake on obstructive lung disorder

<p>Abstract</p> <p>Background and objective</p> <p>This study examined whether zinc intake was associated with lower risk of smoking-induced obstructive lung disorder through interplay with cadmium, one of major toxicants in cigarette smoke.</p> <p>Methods</p> <p>Data were obtained from a sample of 6,726 subjects aged 40+ from the Third National Health and Nutrition Examination Survey. The forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured using spirometry. Gender-, ethnicity-, and age-specific equations were used to calculate the lower limit of normal (LLN) to define obstructive lung disorder as: observed FEV1/FVC ratio and FEV1 below respective LLN. Zinc intake was assessed by questionnaire. Logistic regression analysis was applied to investigate the associations of interest.</p> <p>Results</p> <p>The analyses showed that an increased prevalence of obstructive lung disorder was observed among individuals with low zinc intake regardless of smoking status. The adjusted odds of lung disorder are approximately 1.9 times greater for subjects in the lowest zinc-intake tertile than those in the highest tertile (odds ratio = 1.89, 95% confidence interval = 1.22-2.93). The effect of smoking on lung function decreased considerably after adjusting for urinary cadmium. Protective association between the zinc-to-cadmium ratio (log-transformed) and respiratory risk suggests that zinc may play a role in smoking-associated lung disorder by modifying the influence of cadmium.</p> <p>Conclusions</p> <p>While zinc intake is associated with lower risk of obstructive lung disorder, the role of smoking cession and/or prevention are likely to be more important given their far greater effect on respiratory risk. Future research is warranted to explore the mechanisms by which zinc could modify smoking-associated lung disease.</p

A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences

Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P= 1.2 × 10−4). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7–2.3 for lung cancer(LC;P= 4.0 × 10−4), chronic obstructive pulmonary disease (COPD;P= 9.3 × 10−4), peripheral artery disease (PAD;P= 0.090) and abdominal aortic aneurysms (AAAs; P= 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49,P= 2.2 × 10−4), COPD (OR = 3.22,P= 2.9 × 10−4), PAD (OR = 3.47,P= 9.2 × 10−3) and AAA (OR = 6.44, P= 6.3 × 10−3). Joint analysis of the four smoking-related diseases reveals significant association (P= 6.8 × 10−5), particularly for early-onset cases (P=2.1 × 10−7). Our results are in agreement with functional studies showing that the human α4β2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation