Number Of Environmental Risk Factors Research Articles

Risk factors for the development of arterial hypertension in children and young people in present-day developments

In modern society, there is an intensive increase in the incidence of hypertension among young people, which is mainly due to lifestyle features and associated risk factors. Purpose. To analyze the results of Russian and foreign scientific research concerning the study of risk factors in the development of hypertension in children and young people. Material and methods. A qualitative analysis of the current data available in the literature on the risk factors of hypertension and its prevention has been carried out. Results. It has been established that the occurrence of arterial hypertension in childhood is influenced not only by hereditary factors, but also by a number of environmental risk factors. Conclusion. Further research is needed to study new and established risk factors that need to be considered when conducting primary prevention of the disease in children and young people from the high-risk group.

Formulation and Evaluation of Micro Beads of Clonidine for the Treatment of Anxiety and Hypertensive Disorder

A chronic medical condition known as hypertension (HT) is characterised by persistently high blood pressure (BP) in the arteries. Although HT is initially asymptomatic, it eventually develops into a significant risk factor for renal, cardiovascular, and cerebrovascular conditions, which in turn are major contributors to morbidity and mortality in industrialised nations. A complicated disorder called HT is thought to affect more than one-fourth of adult humans worldwide. Both its pathophysiology (primary and secondary HT) and the measurements of the resting blood pressure (elevated systolic, diastolic, and pulse pressure) are used to categories it. It results from a complex interplay between genes and a number of environmental risk factors, including as ageing, smoking, inactivity, being overweight or obese, eating too much salt, stress, depression, and anxiety. Millions of people are affected by anxiety and depressive disorders each year, which are the most often diagnosed mental illnesses. These conditions are both characterised by emotional, cognitive, psychomotor, and neurovegetative symptoms. Additionally, stress at work has been identified as a significant risk factor for heart disease (CVD) and HT. Despite the fact that numerous writers have looked into and proposed connections between HT, stress, anxiety, and depression over the past few decades, a complete knowledge of the underlying pathophysiological mechanisms has not yet been attained, particularly with regards to young people. The purpose of this study was to examine the role that stress and anxiety from the workplace play in the HT development of young students of health care professions as well as any potential links to early CVDs.
 Keywords: Blood pressure, Anxiety, Work-related stress, Students, Health care professions, Health promotion, Workplace, Occupational medicine

The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review.

Neural tube defects (NTDs) are birth defects that arise during embryogenesis when normal neural tube closure fails to occur. According to the World Health Organization, NTDs are detected annually in approximately 300,000 neonates worldwide. The exact etiology of NTDs remains complex and poorly understood. It is generally agreed that most NTD cases are of multifactorial origin, having a combination of multiple genes and a number of environmental risk factors. The role of folic acid, vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs, has also been extensively studied. This knowledge synthesis brings together different types of evidence to update the role of vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs. Following a PubMed search and screening for relevant articles, we included 40 studies in our review (30 case-control studies, 3 cross-sectional studies, 5 cohort studies, and 2 case reports). The available data showed that vitamin B12 levels were decreased in mothers and infants in NTD groups compared with control groups. Holo-transcobalamin, the active form of vitamin B12, was also found in lower levels in mothers with NTD-affected infants. Several studies reported elevated homocysteine levels in mothers and infants in NTD groups. Additionally, numerous studies reported links between genetic variants and increased NTD risk. These genes include GIF, LRP2, CUBN, TCb1R, MTHFR, and others. Several maternal factors have also been linked with significant NTD risk such as BMI, maternal diet, air pollutants, low maternal age, and many others. The majority of studies on NTDs have focused on the role of folic acid, hence there is a need for well-designed studies on the role of other risk factors like vitamin B12 deficiency in the etiology of NTDs.

Impact of Environmental Factors on the Prevalence Changes of Allergic Diseases in Elementary School Students in Ulsan, Korea: A Longitudinal Study.

We examined the effect of long-term changes in environmental factors on the prevalence of allergic diseases in elementary school students in Ulsan, Korea. This longitudinal study was conducted among 390 students who were enrolled from three elementary schools in Ulsan in both the first (2009–2010) and second survey (2013–2014). The International Study of Asthma and Allergies in Childhood questionnaire was used to determine the prevalence of allergic diseases and hazardous environmental factors. Generalized estimating equations (GEE) were used to investigate the impact of environmental factors on the change in the prevalence of allergic diseases. The survey revealed that an increased risk of allergic rhinitis was associated with exposure to secondhand smoke, the remodeling of a room, the replacement of wallpaper or flooring, the use of a humidifier, and irritation symptoms of air pollution. Atopic dermatitis was associated with the relocation to or repairs of a new house, and allergic conjunctivitis was associated with low levels of weekly physical activity, the use of insecticides, and irritation symptoms of air pollution. The results indicate that (1) allergic rhinitis and atopic dermatitis are associated with indoor pollution, (2) allergic conjunctivitis is associated with exposure to indoor chemical compounds and low levels of weekly physical activity. This study suggested that the proper evaluation and decrease in the number of environmental risk factors could effectively manage allergic diseases.

T81. MULTIPLE DRUG USE IN SCHIZOPHRENIA - THE ROLE OF EARLY ENVIRONMENTAL RISK ACCUMULATION AND GENETIC PREDISPOSITION

BackgroundDrug (ab)use and substance use disorders are frequently observed in patients with psychiatric illness, but the underlying causes remain widely unknown. A number of environmental risk factors have been proposed to affect the use of one or multiple drugs in the general population and adolescents. Whereas most previous studies focused on the influence of single risk factors on the use of one or a few selected drugs, the effect of accumulated environmental risk in early life on multiple drug use remains to be studied. Similarly, evidence on genetic susceptibility to the (ab)use of a single drug, e.g. nicotine, alcohol, cocaine, is abundant, while the role of genetic predisposition for multiple drug use - in particular during early life - is yet to be explored. Thus, the current work aims to study the role of environmental as well as genetic risk factors for multiple drug abuse (‘polytoxicomania’) in a large sample of schizophrenic/schizoaffective patients.MethodsInformation from ~2000 schizophrenia/schizoaffective patients on (preadult) multiple drug use (> 2 drugs) and environmental risk factors was extracted from the Göttingen Research Association for Schizophrenia (GRAS) data collection – currently the largest data base of deeply phenotyped patients with schizophrenia/schizoaffective disorder or other neuropsychiatric diseases. In addition, genetic data from these patients and 2111 healthy blood donors were used in a novel genetic approach that employs multiple genome-wide association studies (GWAS) to identify genetic associations with preadult multiple drug use. Genotyping was performed on a semi-custom Axiom MyDesign Genotyping Array (Affymetrix, Santa Clara, CA, USA), based on a CEU (Caucasian residents of European ancestry from UT, USA) marker backbone.ResultsThe accumulation of environmental risk factors, i.e. sexual abuse, physical abuse, migration, urbanicity, together with alcohol and cannabis consumption as secondary risk factors, in early life (< 18 years) were strongly associated with lifetime multiple drug use (p = 3.48 x 10^-44, extreme group comparison odds ratio (OR) = 31.8). When the sample was split into preadult and adult multiple drug users, there was a remarkable association of the number of preadult environmental risk factors with preadult multiple drug use (p = 1.12 x 10^-25, OR = 243.6). Furthermore, preadult environmental risk accumulation strongly predicted onset of multiple drug use in adulthood (> 18 years; p = 6.27 x 10^-18, OR = 19.4). The application of the novel genetic approach yielded 35 single-nucleotide variants (SNPs) that potentially confer susceptibility to preadult multiple drug use. Out of these, 14 were located in gene-coding regions. Interestingly, 9 of these genes are implicated in neuronal development/function or metabolite transport/transformation. Additional gene-based analyses identified another 4 genes relevant for metabolite transport/transformation as well as 4 genes that play a role in hypoxia signaling.DiscussionThe present results show that an accumulation of environmental risk factors during early life (< 18 years) is a strong predictor of multiple drug use during adolescence and later life. These findings suggest that exposure to accumulated environmental risk during early life is not only associated with violent aggression – as previously reported by our lab – but is also an important predictor of multiple drug use. Moreover, we present first evidence of a genetic susceptibility to preadult multiple drug use, which will benefit from future replication in suitable samples of patients with mental illness or the general population.

Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort: The Hisayama Study.

Background and Purpose- Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods- A total of 3038 subjects aged ≥40 years were followed up for 10 years (2002-2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results- During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels (P for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16-5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors (P for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04-2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions- A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.

Environmental risk factors associated with falls among older people living in long-term aged care facilities: a prospective study

BackgroundFalls are the most common safety problem among older people living in long-term aged care facilities in China. Unsupportive environments can increase the risk of falls among this population. We aimed to understand the distribution of environmental risk factors in long-term aged care facilities and their associations with falls among residents. MethodsThe environmental risk factors in 25 long-term aged care facilities in Changning, Shanghai, were investigated on site using a 75-item questionnaire on potential fall-related risk factors. Residents in participating facilities were interviewed and prospectively followed up for 1 year to ascertain the occurrence of falls. Univariate and multivariate analyses were applied to measure the associations between environmental exposures and falls. FindingsBetween Nov 1, 2017, and Dec 31, 2018, 739 residents were interviewed at baseline and 605 completed 1-year follow-up. 132 (22%) of 605 participants had at least one fall during follow-up. The number of environmental risk factors in each care facility ranged from two to 22 (mean 11 [SD 5]). The three most common factors, which were significantly associated with the occurrence of falls, were inadequate or inappropriate handrails (24 [96%] facilities; risk ratio [RR] for fall occurrence 1·878 [95% CI 1·128–3·126]), unsafe ground (23 [92%]; 2·496 [1·111–5·606]), and insufficient lighting (21 [84%]; 2·008 [1·103–3·656]). Risk factors were most frequently distributed in bedrooms (in 24 [96%] facilities), shared toilets or showers (20 [80%]), and individual toilets or showers (17 [68%]). On univariate analysis, falls were significantly associated with the presence of environmental risk factors in corridors (RR 1·571 [1·058–2·334]), elevators (1·826 [1·224–2·724]), and living rooms (1·843 [1·249–2·720]). After adjusting for demographics and individual risks of falls by Morse Scale, residents in facilities with eight or more environmental factors had significantly increased risk of falls (adjusted RR 2·207 [1·378–3·534]). InterpretationEnvironmental risk factors in long-term aged care facilities are associated with increased risk of falls among residents. Improving lighting and ground safety and installing adequate handrails, especially in corridors, elevators, and living rooms, could reduce the incidence of falls. FundingShanghai Municipal Commission of Health and Family Planning (grant number 201640040), Chinese Center for Disease Control and Prevention.

Examining the link between dose-dependent dietary iron intake and Alzheimer’s disease through oxidative stress in the rat cortex

BackgroundNeurodegenerative diseases such as Alzheimer's and Parkinson's disease are characterized by the progressive deterioration of the structure and function of the nervous system. A number of environmental risk factors including potentially toxic elements such as iron, lead to negative effects on many metabolic reactions as well as neuroprotection. The aim of this study is to reveal whether long-term iron overload is one of the underlying factors in the pathogenesis of Alzheimer's disease (AD). Methods15 young-adult male rats were randomly divided into 5 groups treated with iron through drinking water for 4 months. Following feeding, the iron content, reduced glutathione (GSH), and hydrogen peroxide (H2O2) levels of cortex tissues were measured. Specific enzyme activities were determined spectrophotometrically. mRNA expression profiles were measured using real-time PCR (qPCR). ResultsIron levels were elevated in case of non-toxic (0.87 and 3 μg/mL) iron administration. However, no changes were observed in toxic (30 and 300 μg/mL) iron administration. GSH and H2O2 levels altered with long-term iron overload. Glutathione peroxidase (GPx) enzyme activities significantly increased in all groups, while glutathione S-transferase (GST) activity increased only in case of 0.87 and 30 μg/mL iron administration. Expression levels of neuroprotective and AD-related genes were altered by 3 μg/mL iron overload in a dose-dependent manner. The expression and activity of acetylcholinesterase (AChE) were elevated at 3 μg/mL iron concentration. ConclusionThe findings of the present study allow us to conclude that long-term dietary iron intake, especially at a dose of 3 μg/mL demonstrates negative effects on the rat cortex by provoking antioxidant metabolism and AD pathology in a dose-dependently.

Association of residential air pollution, noise, and greenspace with initial ischemic stroke severity.

Background and PurposeA number of environmental risk factors of acute ischemic stroke have been identified, but few studies have evaluated the influence of the outdoor environment on stroke severity. We assessed the association of residential ambient fine particulate matter air pollution (PM2.5), noise, and surrounding greenspace with initial stroke severity. MethodsWe obtained data on patients hospitalized with acute ischemic stroke from a hospital-based prospective stroke register (2005–2014) in Barcelona. We estimated residential PM2.5 based on an established land use regression model, greenspace as the average satellite-based Normalized Difference Vegetation Index (NDVI) within a 300 m buffer of the residence, and daily (Lday), evening (Levening), night (Lnight) and average noise (Lden) level at the street nearest to the residential address using municipal noise models. Stroke severity was assessed at the time of hospital presentation using the National Institute of Health Stroke Scale (NIHSS).We used logistic regression and binomial models to evaluate the associations of PM2.5, greenspace, and noise with initial stroke severity adjusting for potential confounders. ResultsAmong 2761 patients, higher residential surrounding greenspace was associated with lower risk of severe stroke (OR for NIHSS>5, 0.75; 95% CI: 0.60–0.95), while, living in areas with higher Lden was associated with a higher risk of severe stroke (OR, 1.30; 95% CI: 1.02–1.65). PM2.5 was not associated with initial stroke severity. ConclusionsIn an urban setting, surrounding greenspace and traffic noise at home are associated with initial stroke severity, suggesting an important influence of the built environment on the global burden of ischemic stroke.

Autism spectrum disorder.

This article is based on key recent published literature including international guidelines and relevant reviews and meta-analyses. Authors have also supplemented this material with their own clinical experience. There is an agreement that autism spectrum disorder (ASD) have a strong hereditary component. There is also a consensus that the reported prevalence estimates have increased in the last 5 years. There is strong support for using the broader spectrum disorder conceptualization of the DSM-5. Higher public awareness of ASD has generated several controversial theories of causation. We review a number of environmental risk factors receiving media attention including: vaccines, mercury, heavy metal exposure and Selective Serotonin Uptake Inhibitors (SSRIs). Popular yet controversial treatment interventions are discussed. Early diagnostic screening tools are also addressed. There is increasing scientific interest in identifying biomarkers of autism with potential for early diagnosis, prognostic indicators and predictive treatment responses. We review evidence from genetics, neuroimaging and eye tracking as candidate biomarkers. Family studies point to a strong hereditary component in the aetiology of autism. However these studies have not established 100% concordance rates, suggesting a role for environmental factors. The gene-environment interplay has not received enough attention in scientific research. This represents an important new avenue for research in ASD.

Researchers Sum Up Current Knowledge of Bipolar Disorder, Call for More Study

Researchers Sum Up Current Knowledge of Bipolar Disorder, Call for More Study

92 - Chronic Lead Exposure Induces Cochlear Oxidative Stress and Impairs Hearing

Oxidative stress plays a pivotal role in mediating hearing loss induced by exposure to a number of environmental risk factors. Elevated levels of lead is one of the commonly encountered risk factor in the urban environment. Though lead exposure damages the sensory, vascular, and neuronal components of the cochlea, it is not known whether oxidative stress mediates its ototoxic effects. The aim of this study is to delineate the redox mechanism underlying lead-induced auditory dysfunction. Young-adult C57BL/6 mice were exposed to: 1) control conditions or 2) 2 mM lead acetate in drinking water for 28 days. Blood lead levels were measured by inductively coupled plasma mass spectrometry analysis (ICP-MS), lead-induced cochlear oxidative stress was assessed using targeted gene arrays, and hearing thresholds were assessed by recording auditory brainstem responses. Lead exposure significantly increased the blood lead levels to 293 ± 67 ppb. However, the body weight, appearance, and behavior of the lead-exposed mice were similar to that of the controls. This suggested that the exposure level was probably moderate for young-adult mice, and was not capable of inducing severe toxic effects. Nevertheless, lead exposure at this level downregulated cochlear Sod1, Gpx1, and Gstk1, which encode critical antioxidant enzymes, and upregulated ApoE, Hspa1a, Ercc2, Prnp, Ccl5, and Sqstm1, which are indicative of cellular apoptosis. In addition, exposure to lead induced 8-12 dB shifts in hearing thresholds. Collectively, these findings suggest that chronic exposure to even moderate levels of lead induces cochlear oxidative stress and causes hearing loss.

The relationship between environmental exposures and hormonal abnormalities in pregnant women: An epidemiological study in Yazd, Iran.

The process of industrialization and lifestyle changes have gradually exposed human ‎societies to a larger number of environmental risk factors, which may cause hormonal ‎abnormalities and congenital anomalies. The current study aimed to investigate the relationship ‎between environmental factors and hormonal abnormalities among pregnant women in Yazd, ‎Iran. A hundred participants were randomly selected from among a group of pregnant women. According to the screening tests (AFP, free β-‎HCG, uE3, PAPP-A, and inhibin-A) performed at the genome clinic in Yazd in 2016, the risk of Down Syndrome (DS) was sufficiently high in this group of pregnant women from which the participants were selected. A ‎questionnaire was used to collect data on the degree of the participants' exposure to pesticides ‎at home, use of canned and fast foods, and consumption of greenhouse fruits. The collected data were ‎analyzed by One-way ANOVA and Kruskal-Wallis Test. The mean of Multiple of Median (MoM) for inhibin-A was significantly higher among pregnant ‎women who often or always used pesticides at home (p=0.047). The mean MoM ‎for free β-HCG was significantly higher among pregnant women who often or always used canned ‎foods (p=0.024). Finally, the mean MoM for uE3 (1.85±1.30) was significantly higher among ‎pregnant women who never consumed greenhouse fruits (p=0.003). It can be concluded that it is possible to reduce environmental exposures affecting hormonal abnormalities among pregnant women by improving nutritional patterns, minimizing the use of pesticides at home, and reducing the intake of canned foods and greenhouse fruits.

Promising rodent models in Parkinson's disease

BackgroundIn the past decade, the study of the pathogenic mechanisms underlying neurodegeneration in Parkinson's disease (PD) has revealed a genetic component, often associated with a number of environmental risk factors. Animal models have improved our understanding of disease pathogenesis, providing significant insights into the understanding of novel molecular pathways. Each model has its own specific features and limitations, and the choice of the most appropriate one depends on the specific question that has to be answered. AimTo provide an overview of some of the models supporting the hypothesis that early synaptic dysfunction represents a central event in the course of the disease. DevelopmentAlong with “classical” models, based on the administration of neurotoxins and capable of replicating the neuropathological hallmarks of the disease, a number of genetic models, reproducing the disease-causing mutations of monogenic forms of familial PD, have been generated. More recently, novel models have been developed, based on the combination of a toxic insult together with PD mutations, allowing for the identification of dysfunction at a prodromal disease stage. ConclusionsThe development and characterization of new models is crucial for a better understanding of PD related-synaptopathy, and hold promise for the identification of novel therapeutics.

Evaluation of Environmental Risk Factors for Type 2 Diabetes in Sint Maarten

A number of environmental risk factors have been reported to be associated with elevated blood glucose and diabetes. However, these associations have primarily been explored in Western populations and few studies have examined diabetic risk factors in novel populations such as the Caribbean. We examined whether exercise and food consumption is associated with blood glucose levels in the Caribbean population of Sint Maarten. Using cross-sectional data from Project HELP (Health, Education, Literacy, and Prevention), a collaboration between the American University of the Caribbean School of Medicine and Sint Maarten Ministry of Health, we estimated two logistic regression models predicting elevated blood glucose. The adjusted model included demographic, biological, and social/ behavioral covariates. Unhealthy food consumption was associated with decreased odds of elevated blood glucose in the first model (OR=0.19, p=0.04) but not significant in the adjusted model. All other factors were not significantly associated with blood glucose. It seems that the traditional environmental risk factors – such as exercise and diet – associated with blood glucose in most Western populations are not significant in Sint Maarten. Further research must be conducted to determine appropriate risk factors for this population and possibly other Caribbean populations.

Schizophrenia: a consequence of gene-environment interactions?

Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors (e.g., social stress and cannabis use). It is the combined action of multiple genes of small effect size (Owen et al., 2005) and a number of environmental risk factors (McGrath et al., 2004), which causes the development of this mental disorder (Mackay-Sim et al., 2004). This is conceptualized in the “Two-Hit Hypothesis” of schizophrenia, which predicts that genetic and environmental risk factors interactively (GxE interaction) cause the development of the disorder (Bayer et al., 1999; Caspi and Moffitt, 2006). GxE interactions occur when the expression of an individual's genetic predisposition is dependent on the environment they are living in or when environmental influences on a trait differ according to an individual's genome (Tsuang et al., 2004). Human studies have confirmed that nature and nurture are both important in the development of schizophrenia: the concordance rate in monozygotic twins is only around 50% (Tsuang et al., 2001) and genome wide association studies fail to identify major genetic candidates for schizophrenia (Sanders et al., 2008) suggesting an important role of environmental factors in the development of this disorder.

Environment and the Inflammatory Bowel Diseases

Inflammatory bowel diseases (IBD), which consists of Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. In genetically susceptible individuals, the interaction between environmental factors and normal intestinal commensal flora is believed to lead to an inappropriate immune response that results in chronic inflammation. The incidence of IBD have increased in the past century in developed and developing countries. The purpose of the present review is to summarize the current knowledge of the association between environmental risk factors and IBD. A number of environmental risk factors were investigated including smoking, hygiene, microorganisms, oral contraceptives, antibiotics, diet, breastfeeding, geographical factors, pollution and stress. Inconsistent findings among the studies highlight the complex pathogenesis of IBD. Additional studies are necessary to identify and elucidate the role of environmental factors in IBD etiology.

Risk factors for current wheezing and its phenotypes among elementary school children

Accumulating evidence suggests, asthma includes many phenotypes with varying clinical and prognostic features. Epidemiological surveys documented a number of environmental risk factors for the development of asthma and interestingly these differ between and within countries, suggesting that the differences may be related with the different distribution of asthma phenotypes. This study aimed to investigate risk factors of current wheezing (CW) and different wheezing phenotypes in elementary school children. Six thousand nine hundred sixty-three 9- to 11-year-old children of a previous multicenter survey where the methodology of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase-II was used were analyzed. Wheezing phenotypes were defined as wheezing with rhinitis (RW), wheezing with rhinoconjunctivitis (RCW), atopic wheezing (AW), non-atopic wheezing (NAW), and frequent wheezing (FW) (≥4/year wheezing episodes). The prevalence of CW was 15.8% and among these, 22.4%, 67.3%, 45.9%, 20.5%, and 79.5% were classified as FW, RW, RCW, AW, and NAW, respectively. History of parental asthma/allergic rhinitis, coexistence of other allergic diseases, presence of mold and dampness in the house lived during the first year of life and maternal smoking in pregnancy were found to be risk factors for most phenotypes (odds ratio (OR) ranged from 1.43 to 3.56). Number of household in the last year (OR = 1.14), prematurity (OR = 2.08), and duration of breastfeeding (OR = 1.02) per additional month were found to be risk factor for FW, AW, and RCW, respectively. Beside common risk factors for the development of asthma and its phenotypes, certain risk factors appeared to play a role in the development of phenotypic characteristics of asthma. These findings support our hypothesis that each phenotype has not only different clinical characteristics but also has different roots.

Conceptualizing Schizophrenia Through Attenuated Symptoms in the Population

Conceptualizing Schizophrenia Through Attenuated Symptoms in the Population

Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes

Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.