Genome-wide association studies identify CHRNA5/3 and HTR4 in the development of airflow obstruction.

Rationale: Genome-wide association studies (GWAS) have identified loci influencing lung function, but fewer genes influencing chronic obstructive pulmonary disease (COPD) are known.

Objectives: Perform meta-analyses of GWAS for airflow obstruction, a key pathophysiologic characteristic of COPD assessed by spirometry, in population-based cohorts examining all participants, ever smokers, never smokers, asthma-free participants, and more severe cases.

Methods: Fifteen cohorts were studied for discovery (3,368 affected; 29,507 unaffected), and a population-based family study and a meta-analysis of case-control studies were used for replication and regional follow-up (3,837 cases; 4,479 control subjects).

Vitamin D deficiency, smoking, and lung function in the Normative Aging Study.

Rationale: Vitamin D has immunomodulatory and antiinflammatory effects that may be modified by cigarette smoke and may affect lung function.

Objectives: To examine the effect of vitamin D deficiency and smoking on lung function and lung function decline.

Methods: A total of 626 men from the Normative Aging Study had 25-hydroxyvitamin D levels measured at three different times between 1984 and 2003 with concurrent spirometry.

Effect of vitamin D and inhaled corticosteroid treatment on lung function in children.

Rationale: Low vitamin D levels are associated with asthma and decreased airway responsiveness. Treatment with inhaled corticosteroids improves airway responsiveness and asthma control.

Objectives: To assess the effect of vitamin D levels on prebronchodilator FEV(1), bronchodilator response, and responsiveness to methacholine (PC(20), provocative concentration of methacholine producing a 20% decline in FEV(1)) in patients with asthma treated with inhaled corticosteroids.

Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene.

Bronchodilator response (BDR) is an important asthma phenotype that measures reversibility of airway obstruction by comparing lung function (i.e. FEV(1)) before and after the administration of a short-acting β(2)-agonist, the most common rescue medications used for the treatment of asthma.

Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study.

Preterm birth affects over 12% of all infants born in the US yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during 1(st) trimester (n=914) and 2(nd) trimester (n=922), and from venous cord blood at delivery (n=557), we measured LINE-1 by pyrosequencing (expressed as %5 methyl cytosines within the LINE-1 region analyzed [%5mC]).

Vitamin D deficiency in pregnancy and gestational diabetes mellitus.

Objective: We examined the association of second-trimester maternal plasma 25-hydroxyvitamin D (25[OH]D) during pregnancy with gestational diabetes mellitus (GDM).

Study Design: Among 1314 pregnant women who participated in Project Viva, a birth cohort study, we measured 25(OH)D levels at 26-28 weeks gestation during GDM screening using a 1-hour 50-g glucose challenge test.

Results: We found 25(OH)D levels of <25 nmol/L in 44 of 1087 women (4.

Genome-wide association analysis of circulating vitamin D levels in children with asthma.

Vitamin D deficiency is becoming more apparent in many populations. Genetic factors may play a role in the maintenance of vitamin D levels. The objective of this study was to perform a genome-wide analysis (GWAS) of vitamin D levels, including replication of prior GWAS results.

Plasma 25-hydroxyvitamin D during pregnancy and small-for-gestational age in black and white infants.

Purpose: In a prospective prenatal cohort study, we examined associations of second trimester and cord plasma 25-hydroxyvitamin D (25[OH]D) with small-for-gestational age (SGA) and the extent to which vitamin D might explain black/white differences in SGA.

Methods: We studied 1067 white and 236 black mother-infant pairs recruited from eight obstetrical offices early in pregnancy in Massachusetts. We analyzed 25(OH)D levels using an immunoassay and performed multivariable logistic models to estimate the odds of SGA by category of 25(OH)D level.

Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children.

Rationale: Vitamin D insufficiency (a serum 25(OH)D <30 ng/ml) has been associated with severe asthma exacerbations, but this could be explained by underlying racial ancestry or disease severity. Little is known about vitamin D and asthma in Puerto Ricans.

Objectives: To examine whether vitamin D insufficiency is associated with severe asthma exacerbations in Puerto Rican children, independently of racial ancestry, atopy, and time outdoors.

Folate network genetic variation predicts cardiovascular disease risk in non-Hispanic white males.

Genes functioning in folate-mediated 1-carbon metabolism are hypothesized to play a role in cardiovascular disease (CVD) risk beyond the current narrow focus on the MTHFR 677 C→T (rs1801133) polymorphism. Using a cohort study design, we investigated whether sequence variants in the network of folate-related genes, particularly in genes encoding proteins related to SHMT1, predict CVD risk in 1131 men from the Normative Aging Study. A total of 330 single nucleotide polymorphisms (SNPs) in 52 genes, selected for function and gene coverage, were assayed on the Illumina GoldenGate platform.

Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D.

Background: The adverse effects of corticosteroids on bone mineral accretion (BMA) have been well documented. Vitamin D insufficiency, a prevalent condition in the pediatric population, has also been associated with decreased bone mineral density (BMD).

Objective: We sought to determine whether children with asthma who have lower vitamin D levels are more susceptible to the negative effects of corticosteroids on BMD over time.

African ancestry and lung function in Puerto Rican children.

Background: Puerto Rican and African American subjects share a significant proportion of African ancestry. Recent findings suggest that African ancestry influences lung function in African American adults.

Objective: We sought to examine whether a greater proportion of African ancestry is associated with lower FEV(1) and forced vital capacity (FVC) in Puerto Rican children independently of socioeconomic status, health care access, or key environmental/lifestyle factors.

Gene promoter methylation is associated with lung function in the elderly: the Normative Aging Study.

Lung function is a strong predictor of mortality. While inflammatory markers have been associated with lung function decrease, pathways are still poorly understood and epigenetic changes may participate in lung function decline mechanisms. We studied the cross-sectional association between DNA methylation in nine inflammatory genes and lung function in a cohort of 756 elderly men living in the metropolitan area of Boston.

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: prospective results from a folate-replete population.

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester.

Vitamin D deficiency as a risk factor for childhood allergic disease and asthma.

Purpose Of Review: Over the past 2 years, the number of studies relating vitamin D deficiency and asthma and allergies has increased significantly. The purpose of this review is to update the last review in this journal and examine the evidence of the relationship between vitamin D deficiency and childhood asthma and allergies.

Recent Findings: In the past 2 years since the last review, there have been many studies, both cross-sectional and prospective, that have investigated the effects of vitamin D on the inception and severity of asthma and allergies.

A polymorphism in the thyroid hormone receptor gene is associated with bronchodilator response in asthmatics.

A pro-asthmatic culture milieu and β2-agonist (isoproterenol) were previously shown to regulate the expression of select transcription factors (TFs) within human airway epithelial and smooth muscle cells. This study tests 1116 single-nucleotide polymorphisms (SNPs) across 98 of these TF genes for association with bronchodilator response (BDR) in asthma patients. Genotyping was conducted using the Illumina HumanHap550v3 Beadchip in 403 non-Hispanic White asthmatic children and their parents.

Genetic association between human chitinases and lung function in COPD.

Two primary chitinases have been identified in humans--acid mammalian chitinase (AMCase) and chitotriosidase (CHIT1). Mammalian chitinases have been observed to affect the host's immune response. The aim of this study was to test for association between genetic variation in the chitinases and phenotypes related to chronic obstructive pulmonary disease (COPD).

Association of variants in innate immune genes with asthma and eczema.

Background: The innate immune pathway is important in the pathogenesis of asthma and eczema. However, only a few variants in these genes have been associated with either disease. We investigate the association between polymorphisms of genes in the innate immune pathway with childhood asthma and eczema.

Effects of endotoxin exposure on childhood asthma risk are modified by a genetic polymorphism in ACAA1.

Background: Polymorphisms in the endotoxin-mediated TLR4 pathway genes have been associated with asthma and atopy. We aimed to examine how genetic polymorphisms in innate immunity pathways interact with endotoxin to influence asthma risk in children.

Methods: In a previous analysis of 372 children from the Boston Home Allergens and the Connecticut Childhood Asthma studies, 7 SNPs in 6 genes (CARD15, TGFB1, LY96, ACAA1, DEFB1 and IFNG) involved in innate immune pathways were associated with asthma, and 5 SNPs in 3 genes (CD80, STAT4, IRAK2) were associated with eczema.

Fat-soluble vitamins and atopic disease: what is the evidence?

The prevalence of asthma and other atopic disorders continues to increase worldwide. Examination of the epidemiologic patterns has revealed that this rise has occurred primarily in western, industrialised countries and countries transitioning to this lifestyle. While many changes have occurred in human populations over the years, it has been hypothesised that some of the relevant changes that have led to the rise in asthma and atopic disorders have been the changes from a traditional diet to a more western diet consisting of decreased intake of fruits and vegetables (sources of antioxidant vitamins and carotenoids) leading to decreased intakes of vitamins E and A, and a decrease in sun exposure (e.

Folate network genetic variation, plasma homocysteine, and global genomic methylation content: a genetic association study.

Background: Sequence variants in genes functioning in folate-mediated one-carbon metabolism are hypothesized to lead to changes in levels of homocysteine and DNA methylation, which, in turn, are associated with risk of cardiovascular disease.

Methods: 330 SNPs in 52 genes were studied in relation to plasma homocysteine and global genomic DNA methylation. SNPs were selected based on functional effects and gene coverage, and assays were completed on the Illumina Goldengate platform.

A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.

The genetic risk factors for chronic obstructive pulmonary disease (COPD) are still largely unknown. To date, genome-wide association studies (GWASs) of limited size have identified several novel risk loci for COPD at CHRNA3/CHRNA5/IREB2, HHIP and FAM13A; additional loci may be identified through larger studies. We performed a GWAS using a total of 3499 cases and 1922 control subjects from four cohorts: the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE); the Normative Aging Study (NAS) and National Emphysema Treatment Trial (NETT); Bergen, Norway (GenKOLS); and the COPDGene study.

Genome-wide association study reveals class I MHC-restricted T cell-associated molecule gene (CRTAM) variants interact with vitamin D levels to affect asthma exacerbations.

Background: It has recently been shown that vitamin D deficiency can increase asthma development and severity and that variations in vitamin D receptor genes are associated with asthma susceptibility.

Objective: We sought to find genetic factors that might interact with vitamin D levels to affect the risk of asthma exacerbation.

Methods: We conducted a genome-wide study of gene-vitamin D interaction on asthma exacerbations using population-based and family-based approaches on 403 subjects and trios from the Childhood Asthma Management Program.