Allergic asthma: influence of genetic and environmental factors

Allergic asthma is a chronic airway inflammatory disease in which exposure to allergens causes intermittent attacks of breathlessness, airway hyper-reactivity, wheezing, and coughing. Allergic asthma has been called a "syndrome" resulting from a complex interplay between genetic and environmental factors. Worldwide, >300 million individuals are affected by this disease, and in the United States alone, it is estimated that >35 million people, mostly children, suffer from asthma. Although animal models, linkage analyses, and genome-wide association studies have identified numerous candidate genes, a solid definition of allergic asthma has not yet emerged; however, such studies have contributed to our understanding of the multiple pathways to this syndrome. In contrast with animal models, in which T-helper 2 (T(H)2) cell response is the dominant feature, in human asthma, an initial exposure to allergen results in T(H)2 cell-dependent stimulation of the immune response that mediates the production of IgE and cytokines. Re-exposure to allergen then activates mast cells, which release mediators such as histamines and leukotrienes that recruit other cells, including T(H)2 cells, which mediate the inflammatory response in the lungs. In this minireview, we discuss the current understanding of how associated genetic and environmental factors increase the complexity of allergic asthma and the challenges allergic asthma poses for the development of novel approaches to effective treatment and prevention.     

The influence of genetic and environmental factors among MDMA users in cognitive performance

This study is aimed to clarify the association between MDMA cumulative use and cognitive dysfunction, and the potential role of candidate genetic polymorphisms in explaining individual differences in the cognitive effects of MDMA. Gene polymorphisms related to reduced serotonin function, poor competency of executive control and memory consolidation systems, and high enzymatic activity linked to bioactivation of MDMA to neurotoxic metabolites may contribute to explain variations in the cognitive impact of MDMA across regular users of this drug. Sixty ecstasy polydrug users, 110 cannabis users and 93 non-drug users were assessed using cognitive measures of Verbal Memory (California Verbal Learning Test, CVLT), Visual Memory (Rey-Osterrieth Complex Figure Test, ROCFT), Semantic Fluency, and Perceptual Attention (Symbol Digit Modalities Test, SDMT). Participants were also genotyped for polymorphisms within the 5HTT, 5HTR2A, COMT, CYP2D6, BDNF, and GRIN2B genes using polymerase chain reaction and TaqMan polymerase assays. Lifetime cumulative MDMA use was significantly associated with poorer performance on visuospatial memory and perceptual attention. Heavy MDMA users (>100 tablets lifetime use) interacted with candidate gene polymorphisms in explaining individual differences in cognitive performance between MDMA users and controls. MDMA users carrying COMT val/val and SERT s/s had poorer performance than paired controls on visuospatial attention and memory, and MDMA users with CYP2D6 ultra-rapid metabolizers performed worse than controls on semantic fluency. Both MDMA lifetime use and gene-related individual differences influence cognitive dysfunction in ecstasy users.     

Demographic factors and genetic variation influence population persistence under environmental change

Population persistence has been studied in a conservation context to predict the fate of small or declining populations. Persistence models have explored effects on extinction of random demographic and environmental fluctuations, but in the face of directional environmental change they should also integrate factors affecting whether a population can adapt. Here, we examine the population‐size dependence of demographic and genetic factors and their likely contributions to extinction time under scenarios of environmental change. Parameter estimates were derived from experimental populations of the rainforest species, Drosophila birchii, held in the lab for 10 generations at census sizes of 20, 100 and 1000, and later exposed to five generations of heat‐knockdown selection. Under a model of directional change in the thermal environment, rapid extinction of populations of size 20 was caused by a combination of low growth rate (r) and high stochasticity in r. Populations of 100 had significantly higher reproductive output, lower stochasticity in r and more additive genetic variance (V_A) than populations of 20, but they were predicted to persist less well than the largest size class. Even populations of 1000 persisted only a few hundred generations under realistic estimates of environmental change because of low V_A for heat‐knockdown resistance. The experimental results document population‐size dependence of demographic and adaptability factors. The simulations illustrate a threshold influence of demographic factors on population persistence, while genetic variance has a more elastic impact on persistence under environmental change.     

Summer eczema in exported Icelandic horses: influence of environmental and genetic factors

A cross sectional study was designed to estimate the prevalence of summer eczema (a chronic, recurrent seasonal dermatitis) in exported Icelandic horses and the influence of environmental and genetic factors on the development of the disease.     

Contribution of genetic and environmental factors to variation in body compartments--a twin study in adults

This study aimed at analyzing the contribution of genetic and environmental factors on phenotypic variation of various traits of body composition. Subjects were 30 same-sexed pairs of twins including 20 monozygous (MZ) and 10 dizygous (DZ) pairs, aged 19-62 years. Zygosity was determined by DNA typing and morphological diagnosis. Body composition parameters (fat mass FM, lean body mass LBM, body cell mass BCM, extracellular mass ECM, total body water TBW, extracellular water ECW, and intracellular water ICW) were estimated by tetrapolar bioelectrical impedance analysis. Potential environmental factors influencing body composition (number of children, sporting activity and smoking behaviour) were determined by questionnaires. Heritabilities for traits of body composition were calculated by use of the twin method. Intraclass correlation is > 0.80 for the variation of LBM, BCM, ECM, TBW, ECW, and ICW in both MZ and DZ twins. Estimated heritability (h2) for FM, LBM, BCM, ECW, TBW, ECW, and ICW is 65%, 77%, 79%, 83%, 76%, 68%, and 82%, respectively. The h2 values for FM and LBM are consistent with those reported in other twin studies. For BCM, ECM, ECW and ICW, no comparative h2 estimates exist. Within-pair differences in body compartments do not change with increasing age in MZ and DZ twin pairs (p > 0.05). Stepwise multiple regression analyses indicate that zygosity, age, sex, number of children, sporting level and smoking behaviour do not significantly predict within-pair differences for weight, BMI, FM, LBM, TBW, ECW and ICW (each, p > 0.05). In contrast, sex and the number of children explain together 27% of observed within-pair differences for BCM. Zygosity is the only significant predictor of within-pair differences for ECM and height, explaining 20% (p = 0.008) and 36% of variance, respectively (p < 0.0001). Results indicate that genetic factors exert stronger influences on body composition than the considered environmental traits.     

Genetic estimations for body size characters,development period and development rate in a coccinelid beetle,Harmonia axyridis

Heritabilities and genetic correlations for body size characters and development period in a coccinellid beetle,Harmonia axyridis were estimated by a sib-analysis experiment. Positive genetic correlations were detected between size characters and development rate. If this is upheld in the field, genetic variation would be eliminated, as the loci affecting the characters are supposed to be fixed. However, the results indicated moderate heritabilities for all characters. Possible explanations for the results are discussed.     

Sex differences in genetic and environmental factors contributing to body-height.

Sex differences in the heritability of self-reported body-height in two Finnish twin cohorts were studied by using sex-limitation models. The first cohort was born in 1938-1949 (N = 4873 twin pairs) and the second in 1975-1979 (N = 2374 twin pairs). Body-height was greater in the younger cohort (difference of 3.1 cm for men and 2.9 cm for women). The heritability estimates were higher among men (h2 = 0.87 in the older cohort and h2 = 0.82 in the younger cohort) than women (h2 = 0.78 and h2 = 0.67, respectively). Sex-specific genetic factors were not statistically significant in either cohort, suggesting that the same genes contribute to variation in body height for both men and women. The stronger contribution of environmental factors to body-height among women questions the hypothesis that women are better buffered against environmental stress, at least for this phenotype.     

The controlling factors limiting maximum body size of insects

The purpose of this study is to consider the controlling factors limiting maximum body size of insects. For this analysis, we set up and quantitatively verify the following working hypothesis: insect body sizes can be explained only by the historical changes in the oxygen supply. The present study focuses on the body size of the Protodonata and Odonata. The amount of oxygen needed and that of oxygen entering the insect body was calculated using allometric equations. The theoretical maximum sizes at each geologic time were estimated from palaeo‐atmospheric oxygen partial pressure and compared with the maximum size of known fossilized insects. The historical change in fossilized insect sizes was much larger than that in theoretical sizes. Additionally, from the Jurassic, despite an increase in the partial pressure of oxygen, which would theoretically increase maximum size, the maximum size of fossilized insects became smaller. These findings are inconsistent with the expectations of the working hypothesis. Oxygen supply is likely to partially limit the maximum size of insects with additional factors.     

Reproductive strategies of primates: The influence of body size and diet on litter size

The frequency of multiple births, life history parameters, body size, and diet characteristics were obtained from the literature for 70 primate species. The general pattern within the primate order is to have single infant litters, yet multiple births regularly occur in a number of species in specific phylogenetic groups. Primates which have large litters tend to be small, have short gestation periods and give birth to small infants, which are weaned quickly, and mature rapidly. Species in which multiple births are common also have short interbirth intervals and in the Callitrichidae have males which exhibit paternal care. In addition, they are commonly insectivorous. Although it is difficult to isolate the effects of diet on litter size, independent of body size, analyses suggest that after the influence of body size is statistically removed, as the proportion of insects in the diet increases, animals have larger litters. We suggest that by adopting a mixed diet of insects and fruit primates may be able to ensure access to a seasonally stable food resource that is not greatly restricted by the presence of toxins. This diet would allow a relatively high metabolism and facilitate large litters.     

Genome size and environmental factors in the genus Pinus

Nuclear 1C DNA content in haploid megagametophyte tissue of 18 North American and one exotic Pinus species was determined using scanning microspectrophotometry. The nuclear DNA content in root meristematic cells of Zea mays L. ssp. mays, inbred line Va35 (4C = 10.31 pg) was used as a standard. DNA content measured by microspectrophotometry was verified using laser flow cytometry with two additional standards, Hordeum vulgare cv. Sultan (2C = 11.12 pg) and P. eldarica (2C = 47.30 pg). DNA values obtained by both methods were significantly correlated (r = 0.987). The 1C nuclear DNA content ranged from 21 pg to 31 pg. The ratio of DNA content in embryo tissue of P. eldarica to that in megagametophyte tissue was 1.72 by scanning microspectrophotometry and 1.74 by laser flow cytometry. To date, this is the most comprehensive data set available for North American Pinus species. Relationships between genome size of 18 North American Pinus species and climatic factors and indices of growth were investigated using regression and correlation analyses. Positive correlations were observed between nuclear DNA content and growth indices, minimum seed-bearing age, and seed dimensions. Strong negative correlations were observed between nuclear DNA content and two climatic factors, the lowest mean annual and monthly precipitation (excluding January) and the highest mean monthly spring air temperature. These correlations suggest that the large genome size and its variation in Pinus are adapted responses to the habitats of these species.     

Assessing the correlates of desired family size in Shaanxi,China

Abstract

This exploratory analysis of factors associated with Chinese women's fertility desires uses data on married women between the ages of 18 and 35 who live in Shaanxi Province, China. Analyses using an economic framework found that both rural and urban couples who intended to sign, or who had already signed, the one‐child certificate reported wanting significantly fewer children. However, in rural areas (where 80 per cent of the provincial population lives), education level, living arrangements, participation in an arranged marriage, attitudes regarding the ideal age for marriage, and knowledge of the reasons for the government's fertility policies appear to play a relatively larger role in shaping fertility preferences.     

The influence of body size on measurements of overall cardiac function

The purpose of this study was to determine the best scaling method to account for the effects of body size on measurements of overall cardiac function and subsequently the interpretation of data based on cardiac power output (CPO). CPO was measured at rest (CPO(rest)) and at maximal exercise (CPO(max)) on 88 and 103 healthy but untrained men and women, respectively, over the age range of 20-70 yr. Cardiac reserve (CR) was calculated as CPO(max) - CPO(rest). CPO(rest), CPO(max), and CR were all significantly related to body mass (BM), body surface area (BSA), and lean body mass (LBM). The linear regression model failed to completely normalize these measurements. In contrast, the allometric model produced size-independent values of CPO. Furthermore, all the assumptions associated with the allometric model were achieved. For CPO(rest), mean body size exponents were BM(0.33), BSA(0.60), and LBM(0.47). For CPO(max), the exponents were BM(0.41), BSA(0.81), and LBM(0.71). For CR, mean body size exponents were BM(0.44), BSA(0.87), and LBM(0.79). LBM was identified (from the root-mean-squares errors of the separate regression models) as the best physiological variable (based on its high metabolic activity) to be scaled in the allometric model. Scaling of CPO to LBM(b) (where b is the scaling exponent) dramatically reduced the between-gender differences with only a 7% difference in CPO(rest) and CPO(max) values. In addition, the gender difference in CR was completely removed. To avoid erroneous interpretations and conclusions being made when comparing data between men and women of different ages, the allometric scaling of CPO to LBM(b) would seem crucial.     

Dependence of phenotypic variance in body size on environmental quality

The recent "overhead threshold" model for optimal age and body size at maturity (Day and Rowe 2002 ) predicts that phenotypic variability in adult body size will be low under inferior environmental quality and will increase with improving conditions. The model is, however, based on a potentially restrictive assumption of a monotone increase of fecundity with increasing body size. On the basis of a numerical model, we show that introducing the concept of maximum adult body size changes the predictions of the model. The dependence of variability in adult body size on environmental quality becomes a concave function with a maximum at intermediate values. Depending on the range of environmental conditions considered, one may therefore expect to observe both increasing and decreasing functions. We test the predictions of our model on a literature-based database of 131 insect species covering all major orders. We demonstrate that, in most species, relative phenotypic variation in body size decreases when environment-specific average of adult body size increases. In the majority of cases at least, such a relationship can be interpreted as a decreased relative variation in better growing conditions. With some potentially meaningful exceptions (e.g., females of capital-breeding insects), the general pattern was largely invariable across different taxa, ecological subdivisions, and sexes.