Biomedical subjects

Augusto A Litonjua

Publications and source records attributed to Augusto A Litonjua.

At least 19 recordsLinked to original sources

PubMed2006

Cord blood cytokines and acute lower respiratory illnesses in the first year of life.

OBJECTIVES: Little is known about the relation between cytokine profile at birth and acute lower respiratory illnesses in the first year of life. The purpose of this work was to examine the relation between cytokine secretions by cord blood mononuclear cells and acute lower respiratory illness in a birth cohort of 297 children. METHODS: Cord blood mononuclear cells were isolated, and secretion of interferon-gamma, interleukin-13, interleukin-10, and tumor necrosis factor-alpha at baseline and in response to allergens (Blatella germanica 2 and Dermatophagoides farinae 1) and mitogen (phytohemagglutinin) were quantified using enzyme-linked immunosorbent assay. Acute lower respiratory illness was defined as a parental report of a diagnosis of bronchiolitis, pneumonia, bronchitis, and/or croup by a health care professional in the first year of life. Differences in the levels of cord blood cytokines between children with and without acute lower respiratory illness were examined using 2-sample Wilcoxon tests. Logistic regression models were used to examine the relation between various categories of cord blood cytokines and acute lower respiratory illness. RESULTS: Median levels of interferon-gamma secreted by cord blood mononuclear cells in response to Blatella germanica 2 and Dermatophagoides farinae 1 were higher among children without acute lower respiratory illness as compared with children with acute lower respiratory illness. After adjustment for other covariates, the odds of acute lower respiratory illness was reduced among children in the top category (at or more than the median of detectable values) of interferon-gamma level, significantly so in response to Blatella germanica 2. CONCLUSIONS: In a cohort of children from the general population, we found that upregulated interferon-gamma secretion at birth is associated with reduced risk of acute lower respiratory illness in the first year of life.

Acute Disease↗

PubMed2006

Respiratory illnesses in early life and asthma and atopy in childhood.

BACKGROUND: The relation between respiratory illnesses in early life and the development of asthma and atopy in childhood is incompletely understood. OBJECTIVE: We sought to examine the relationship between respiratory illnesses in early life and atopic diseases at school age. METHODS: We performed a prospective birth cohort study of the relationship between respiratory illnesses in the first year of life and asthma, atopy (sensitization to >or=1 allergen), and allergic rhinitis at school age in 440 children with a parental history of atopy. Logistic regression was used to examine the relationship between respiratory illnesses and asthma, atopy, and allergic rhinitis. The relationship between respiratory illnesses in early life and repeated measures of wheezing between the ages of 1 and 7 years was investigated by using a proportional hazards models. RESULTS: Physician-diagnosed croup (adjusted odds ratio [OR], 0.30; 95% CI, 0.12-0.72) and having 2 or more physician-diagnosed ear infections (adjusted OR, 0.58; 95% CI, 0.35-0.98) in the first year of life were inversely associated with atopy at school age. Physician-diagnosed bronchiolitis before age 1 year was significantly associated with asthma at age 7 years (adjusted OR, 2.77; 95% CI, 1.23-6.22). Recurrent nasal catarrh (>or=3 episodes of a runny nose) in the first year of life was associated with allergic rhinitis at age 7 years (adjusted OR, 2.99; 95% CI, 1.03-8.67). CONCLUSION: The relationship between early-life respiratory illnesses and asthma and atopy is complex and likely dependent on the type of infection and immune response it initiates. CLINICAL IMPLICATIONS: Certain respiratory illnesses in early life modify the risk of atopy and asthma at school age.

Allergens↗

PubMed2006

Uric acid and the development of hypertension: the normative aging study.

Experimental evidence supports a causative role for uric acid in the pathogenesis of hypertension. Prospective studies have variably adjusted for relevant confounders and have been of relatively limited duration. We prospectively examined the relationship between uric acid level and the development of hypertension in the Normative Aging Study, a longitudinal cohort of healthy adult men. Of the 2280 initial men in the Normative Aging Study, 2062 had available information for inclusion in the analysis. Cox proportional hazards model was used to examine the relationship between baseline serum uric acid level and the development of hypertension adjusting for age, body mass index, abdominal circumference, smoking, alcohol, plasma triglycerides, total cholesterol, and plasma glucose. A total of 892 men developed hypertension over a mean of 21.5 years of follow-up. Serum uric acid level independently predicted the development of hypertension in age-adjusted (relative risk [RR]: 1.10; 95% CI: 1.06 to 1.15: P<0.001) and multivariable (RR: 1.05; 95% CI: 1.01 to 1.10; P=0.02) models. Among 1277 men at risk for the development of hypertension at the time of their first serum creatinine measurement, 508 (39.8%) developed hypertension over a mean of 10.3+/-5.5 years of follow-up. Additionally adjusting for calculated glomerular filtration rate in this subset, serum uric acid remained associated with the development of hypertension (RR: 1.06; 95% CI: 1.01 to 1.12; P=0.03). The baseline serum uric acid level is a durable marker of risk for the development of hypertension. The association is independent of elements of the metabolic syndrome, alcohol intake, and renal function.

Adult↗

PubMed2006

Predictors of cord blood IgE levels in children at risk for asthma and atopy.

BACKGROUND: Increased cord blood IgE levels, in conjunction with a family history of atopy, are associated with the development of allergic diseases in children. However, little is known about predictors of cord blood IgE levels. OBJECTIVE: Our objective was to identify predictors of cord blood IgE levels among infants at increased risk of atopy. METHODS: Cord blood IgE levels were measured in 874 infants who were screened for participation in a birth cohort. Questionnaires were administered after birth of the infant, and maternal and cord blood was obtained for measurement of IgE levels. Logistic and tobit regression models were used to study the association between perinatal factors and cord blood IgE levels. RESULTS: In multivariable models infant male sex, increased maternal total IgE level, maternal allergen sensitization, Hispanic ethnicity, and residence in low-income areas were associated with detectable or increased cord blood IgE levels, whereas increasing maternal age was associated with undetectable or lower cord blood IgE levels. Although maternal smoking during pregnancy was positively associated with cord blood IgE levels in univariable models, the effect did not persist after adjusting for potential confounders. CONCLUSION: Maternal allergen sensitization, markers of socioeconomic disadvantage and race/ethnicity, maternal age, and infant sex might influence fetal production of IgE. We found no association of maternal parity, mode of delivery, gestational age, or season of birth with cord blood IgE levels. CLINICAL IMPLICATIONS: The identification of these definable familial and environmental factors that predict cord blood IgE levels might help in the early detection of infants at risk for atopic disorders.

Adolescent↗

PubMed2006

Mode of delivery and cord blood cytokines: a birth cohort study.

BACKGROUND: The mechanisms for the association between birth by cesarean section and atopy and asthma are largely unknown. OBJECTIVE: To examine whether cesarean section results in neonatal secretion of cytokines that are associated with increased risk of atopy and/or asthma in childhood. To examine whether the association between mode of delivery and neonatal immune responses is explained by exposure to the maternal gut flora (a marker of the vaginal flora). METHODS: CBMCs were isolated from 37 neonates at delivery, and secretion of IL-13, IFN-gamma, and IL-10 (at baseline and after stimulation with antigens [dust mite and cat dander allergens, phytohemagglutinin, and lipopolysaccharide]) was quantified by ELISA. Total and specific microbes were quantified in maternal stool. The relation between mode of delivery and cord blood cytokines was examined by linear regression. The relation between maternal stool microbes and cord blood cytokines was examined by Spearman's correlation coefficients. RESULTS: Cesarean section was associated with increased levels of IL-13 and IFN-gamma. In multivariate analyses, cesarean section was associated with an increment of 79.4 pg/ml in secretion of IL-13 by CBMCs after stimulation with dust mite allergen (P < 0.001). Among children born by vaginal delivery, gram-positive anaerobes and total anaerobes in maternal stool were positively correlated with levels of IL-10, and gram-negative aerobic bacteria in maternal stool were negatively correlated with levels of IL-13 and IFN-gamma. CONCLUSION: Cesarean section is associated with increased levels of IL-13 and IFN-gamma, perhaps because of lack of labor and/or reduced exposure to specific microbes (e.g., gram-positive anaerobes) at birth.

Journal Article↗

PubMed2006

Transcriptional response to persistent beta2-adrenergic receptor signaling reveals regulation of phospholamban, which alters airway contractility.

Beta(2)-Adrenergic receptors (beta(2)AR) are expressed on airway smooth muscle cells and act to relax the airway on activation by beta-agonists. These agents are utilized for treating asthma but are associated with adverse outcomes. To ascertain the effects of persistent beta(2)AR activation on gene expression, cultured airway smooth muscle cells derived from wild-type (WT) and transgenic mice overexpressing beta(2)AR were subjected to DNA microarray analysis; 319 genes were increased and 164 were decreased. Differential expression was observed in genes from 22 Gene Ontology Slim categories, including those associated with ion transport and calcium ion binding. A 60% decrease (P = 0.008) in phospholamban (PLN), an intracellular Ca(2+) concentration ([Ca(2+)]i)-handling protein that is at a signaling nodal point in cardiomyocytes, was observed in beta(2)AR-overexpressing cells and confirmed at the protein level. To isolate the physiological effect of decreased PLN in airway smooth muscle, airway contraction and relaxation responses were studied in WT and PLN(-/-) mice. PLN(-/-) mice had a markedly reduced constrictive response to methacholine. In contrast, the bronchodilatory effect of beta-agonist was not different between WT and PLN(-/-) mice. These results revealed an unanticipated therapeutic effect of beta-agonists, PLN downregulation, which acts to decrease airway hyperreactivity. Thus agents that inhibit PLN may act synergistically with the bronchodilating action of beta-agonists. A number of other genes related to [Ca(2+)]i are also differentially regulated by beta(2)AR activity, some of which may act to oppose, or augment, the efficacy of chronic beta-agonists. These genes or pathways may also represent additional targets in the treatment of asthma and related obstructive lung diseases.

Airway Resistance↗

PubMed2006

Prenatal, perinatal, and heritable influences on cord blood immune responses.

BACKGROUND: Maternal and perinatal environmental exposures, as well as inherited factors, may influence neonatal immune responses. OBJECTIVE: To determine relations of maternal and perinatal exposures to antigen-specific cord blood lymphoproliferative responses. METHODS: In 427 newborns from a Boston pregnancy/birth cohort, lymphoproliferative responses in cord blood mononuclear cells to stimulation with cockroach (Bla g 2), house dust mite (Der f 1), ovalbumin, and mitogen phytohemagglutinin were measured as stimulation index (SI). We used the Wilcoxon rank sum and chi2 tests to evaluate predictors of ovalbumin SI as a continuous ranked or dichotomous outcome. We used t test and Spearman correlation for univariate testing and linear regression to evaluate predictors of natural log-transformed Bla g 2, Der f 1, and phytohemagglutinin SI. Logistic multivariate regression was applied to evaluate predictors of Bla g 2, Der f 1, and phytohemagglutinin SI dichotomized at 2 or at the median for phytohemagglutinin. RESULTS: Maternal smoking during pregnancy, inadequate or excessive maternal weight gain during pregnancy, neonate black race/ethnicity (compared with white), and Apgar score less than 8 were each independently associated with increased cord blood mononuclear cell proliferative responses to stimulation with Bla g 2 and/or Der f 1. Maternal history of asthma was associated only with increased lymphoproliferative response to ovalbumin stimulation. CONCLUSIONS: Distinct fetal and perinatal exposures and black race/ethnicity may be associated with increased cord blood lymphoproliferative responses. The implications of these findings for future development of allergy or asthma are, as yet, unknown.

Antigens↗

PubMed2006

Maternal antioxidant intake in pregnancy and wheezing illnesses in children at 2 y of age.

BACKGROUND: Low intakes of dietary antioxidants may contribute to increases in asthma and allergy. OBJECTIVE: We investigated the association of maternal total intakes (foods + supplements) of 10 antioxidant nutrients during pregnancy with wheezing and eczema in 2-y-old children. DESIGN: Subjects were 1290 mother-child pairs in an ongoing cohort study. Maternal dietary and supplement intakes were assessed by using a validated food-frequency questionnaire administered in the first and second trimesters. Antioxidant nutrient intakes were calculated, and the mean for each nutrient was considered to be the exposure during pregnancy. The outcomes of interest were any wheezing by the child during either the first or second year of life, recurrent wheezing in both years, and eczema in either the first or second year. RESULTS: No association was observed between maternal total intake of any antioxidant nutrient and eczema. In multivariate logistic regression models, the highest quartile compared with the lowest quartile of maternal total intakes of vitamin E [odds ratio (OR): 0.70; 95% CI: 0.48, 1.03] and zinc (OR: 0.59; 95% CI: 0.41, 0.88) was inversely associated with any wheezing at 2 y of age (P for trend = 0.06 and 0.01 over quartiles of intake for vitamin E and zinc, respectively). Similar results were obtained for recurrent wheezing at 2 y of age with vitamin E (OR: 0.49; 95% CI: 0.27, 0.90) and zinc (OR: 0.49; 95% CI: 0.27, 0.87) (P for trend = 0.05 and 0.06 over quartiles of intake for vitamin E and zinc, respectively). CONCLUSION: Our results suggest that higher maternal total intakes of antioxidants during pregnancy may decrease the risks for wheezing illnesses in early childhood.

Adult↗

PubMed2006

The significance of beta2-adrenergic receptor polymorphisms in asthma.

PURPOSE OF REVIEW: The gene that encodes the beta2-adrenergic receptor (ADRB2) is one of the most studied candidate genes in asthma. This review examines recent articles of the relationship between ADRB2 polymorphisms and asthma. RECENT FINDINGS: Candidate gene association studies of ADRB2 and asthma have been dominated by analyses of the two common non-synonymous coding single nucleotide polymorphisms, Arg16Gly and Glu27Gly. Published studies have yielded inconsistent results. Three recent meta-analyses on the effects of these two polymorphisms have found no associations with asthma, although there were suggestions of associations with other asthma-related phenotypes, such as nocturnal asthma and asthma severity. Other recent studies have investigated other single nucleotide polymorphisms in this gene (i.e. single nucleotide polymorphisms in the promoter region and other single nucleotide polymorphisms in the coding region). These analyses have investigated the association between these single nucleotide polymorphisms (and haplotypes of these polymorphisms) and asthma-related phenotypes such as lung function, airways hyperresponsiveness, and response to a bronchodilator, and have suggested that certain regions of the gene may be associated with different phenotypes. Results from these studies, however, have also been inconsistent. SUMMARY: Polymorphisms of ADRB2 are not major risk factors for the development of asthma. These polymorphisms are likely to be important, however, in determining drug response. Future studies need to fully characterize all of the variation in the gene and perform comprehensive association studies. Finally, interactions between ADRB2 and other genes in the beta-agonist pathway are an important and active area of research that will shed more light on inter-individual differences in drug response.

Asthma↗

PubMed2006

Sensitization to aeroallergens and airway hyperresponsiveness at 7 years of age.

STUDY OBJECTIVES: To investigate the relationship between current and early life factors and airway responsiveness to inhaled methacholine in children with a median age of 7.0 years. PARTICIPANTS: Study subjects were a subset of a prospective birth cohort of children in the Boston area at high risk for atopy. METHODS: One hundred thirty-one children underwent both skin-prick testing to a panel of aeroallergens and a methacholine challenge test between 6.5 years and 8.8 years of age. Telephone questionnaires were performed at set intervals, and home dust samples were collected in the first year of life. RESULTS: Of the 131 participating children, 51% (67 patients) had at least one positive skin-prick test response and 28% (37 patients) had airway hyperresponsiveness (AHR) [provocative concentration of methacholine causing a 20% fall in FEV(1) of < 4 mg/mL]. After adjusting for relevant covariates, AHR was strongly associated with sensitization to at least four aeroallergens (odds ratio [OR], 13.41; 95% confidence interval [CI], 3.03 to 59.42). In separate adjusted models, sensitization to cat (OR, 14.73; 95% CI, 3.64 to 59.55), dust mite (OR, 5.13; 95% CI, 1.94 to 13.56), cockroach (OR, 4.00; 95% CI, 1.19 to 13.50), and ragweed (OR, 10.08; 95% CI, 2.31 to 44.10) were significant predictors of AHR. However, no relationship was found with early life exposure to perennial aeroallergens or other perinatal and first-year-of-life factors. CONCLUSIONS: Among young children at risk for atopy, sensitization to specific aeroallergens, but not early life exposures, is associated with increased airway responsiveness.

Allergens↗

PubMed2005

The SERPINE2 gene is associated with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a complex human disease likely influenced by multiple genes, cigarette smoking, and gene-by-smoking interactions, but only severe alpha 1-antitrypsin deficiency is a proven genetic risk factor for COPD. Prior linkage analyses in the Boston Early-Onset COPD Study have demonstrated significant linkage to a key intermediate phenotype of COPD on chromosome 2q. We integrated results from murine lung development and human COPD gene-expression microarray studies with human COPD linkage results on chromosome 2q to prioritize candidate-gene selection, thus identifying SERPINE2 as a positional candidate susceptibility gene for COPD. Immunohistochemistry demonstrated expression of serpine2 protein in mouse and human adult lung tissue. In family-based association testing of 127 severe, early-onset COPD pedigrees from the Boston Early-Onset COPD Study, we observed significant association with COPD phenotypes and 18 single-nucleotide polymorphisms (SNPs) in the SERPINE2 gene. Association of five of these SNPs with COPD was replicated in a case-control analysis, with cases from the National Emphysema Treatment Trial and controls from the Normative Aging Study. Family-based and case-control haplotype analyses supported similar regions of association within the SERPINE2 gene. When significantly associated SNPs in these haplotypic regions were included as covariates in linkage models, LOD score attenuation was observed most markedly in a smokers-only linkage model (LOD 4.41, attenuated to 1.74). After the integration of murine and human microarray data to inform candidate-gene selection, we observed significant family-based association and independent replication of association in a case-control study, suggesting that SERPINE2 is a COPD-susceptibility gene and is likely influenced by gene-by-smoking interaction.

Amyloid beta-Protein Precursor↗

PubMed2005

A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease.

We describe a novel variant in the terminal exon of human elastin, c.2318 G > A, resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary disease (COPD). Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate change compromises the ability of the mutant protein to undergo normal elastin assembly. Other functional consequences of this amino acid substitution include altered proteolytic susceptibility of the C-terminal region of elastin and reduced interaction of the exon 36 sequence with matrix receptors on cells. These results suggest that the G773D variant confers structural and functional consequences relevant to the pathogenesis of COPD.

Alternative Splicing↗

PubMed2005

Paternal history of asthma and airway responsiveness in children with asthma.

RATIONALE: Little is known regarding the relationship between parental history of asthma and subsequent airway hyperresponsiveness (AHR) in children with asthma. OBJECTIVES: We evaluated this relationship in 1,041 children with asthma participating in a randomized trial of antiinflammatory medications (the Childhood Asthma Management Program [CAMP]). METHODS: Methacholine challenge testing was performed before treatment randomization and once per year over an average of 4.5 years postrandomization. Cross-sectional and longitudinal repeated measures analyses were performed to model the relationship between PC20 (the methacholine concentration causing a 20% fall in FEV1) with maternal, paternal, and joint parental histories of asthma. Models were adjusted for potential confounders. MEASUREMENTS AND MAIN RESULTS: At baseline, AHR was strongly associated with a paternal history of asthma. Children with a paternal history of asthma demonstrated significantly greater AHR than those without such history (median log(e)PC20, 0.84 vs. 1.13; p = 0.006). Although maternal history of asthma was not associated with AHR, children with two parents with asthma had greater AHR than those with no parents with asthma (median log(e)PC20, 0.52 vs. 1.17; p = 0.0008). Longitudinal multivariate analysis of the relation between paternal history of asthma and AHR using repeated PC20 measurements over 44 months postrandomization confirmed a significant association between paternal history of asthma and AHR among children in CAMP. CONCLUSIONS: Our findings suggest that the genetic contribution of the father is associated with AHR, an important determinant of disease severity among children with asthma.

Adolescent↗

PubMed2005

Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma.

BACKGROUND: Identifying genetic determinants for lung function is important in providing insight into the pathophysiology of asthma. Signal transducer and activator of transcription 3 is a transcription factor latent in the cytoplasm; the gene (STAT3) is activated by a wide range of cytokines, and may play a role in lung development and asthma pathogenesis. METHODS: We genotyped six single nucleotide polymorphisms (SNPs) in the STAT3 gene in a cohort of 401 Caucasian adult asthmatics. The associations between each SNP and forced expiratory volume in 1 second (FEV1), as a percent of predicted, at the baseline exam were tested using multiple linear regression models. Longitudinal analyses involving repeated measures of FEV1 were conducted with mixed linear models. Haplotype analyses were conducted using imputed haplotypes. We completed a second association study by genotyping the same six polymorphisms in a cohort of 652 Caucasian children with asthma. RESULTS: We found that three polymorphisms were significantly associated with baseline FEV1: homozygotes for the minor alleles of each polymorphism had lower FEV1 than homozygotes for the major alleles. Moreover, these associations persisted when we performed an analysis on repeated measures of FEV1 over 8 weeks. A haplotypic analysis based on the six polymorphisms indicated that two haplotypes were associated with baseline FEV1. Among the childhood asthmatics, one polymorphism was associated with both baseline FEV1 and the repeated measures of FEV1 over 4 years. CONCLUSION: Our results indicate that genetic variants in STAT3, independent of asthma treatment, are determinants of FEV1 in both adults and children with asthma, and suggest that STAT3 may participate in inflammatory pathways that have an impact on level of lung function.

Adult↗

PubMed2005

Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase type 9 in asthma: interaction between beta-agonist and corticosteroid pathways.

In asthma, the response to beta-agonists acting at beta2-adrenergic receptors (beta2AR) displays extensive interindividual variation. One effector for airway beta2AR, adenylyl cyclase type 9 (AC9), was considered a candidate locus for predicting beta-agonist efficacy in the absence and presence of corticosteroid treatment. One non-synonymous AC9 polymorphism has been identified, which results in substitution of Met for Ile at amino acid 772. Under standard culture conditions in stably transfected cells, we found decreased catalytic activity of Met772. However, cells cultured in the presence of glucocorticoid expressing Met772 had a significantly increased albuterol-stimulated adenylyl cyclase response (approximately 80%) when compared with those expressing Ile772 (approximately 20%, P=0.02). An equivalent increase in beta2AR expression was observed in both lines due to glucocorticoid, but AC9 expression was unaffected. The hypothesis that Met772-AC9 is associated with an improved albuterol bronchodilator response in asthmatics was investigated in 436 asthmatic children who were followed for 4 years and randomized to receive placebo or the inhaled corticosteroid budesonide. Met772 carriers on budesonide showed a significant improvement in forced expiratory volume in 1 s (P=0.005). Moreover, a highly significant interaction (P=0.002) was found for budesonide treatment and the AC9 polymorphism. These in vitro and human association studies are consistent with this AC9 polymorphism altering albuterol responsiveness in the context of concomitant inhaled corticosteroid administration, which is a common asthma regimen. The Met772-AC9 polymorphism represents one of most likely several multi-gene polymorphisms along the receptor-relaxation axis, which together may provide for a composite pharmacogenetic index for asthma therapy.

Adenylyl Cyclases↗

PubMed2005

Lung function in type 2 diabetes: the Normative Aging Study.

BACKGROUND: Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects. METHODS: We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes; Time1, the point when the definition of diabetes was met; and Time2, the most recent follow-up exam. RESULTS: Cases had lower forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV1 or FVC change over time between cases and controls. CONCLUSIONS: Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.

Adult↗

PubMed2005

Attempted replication of reported chronic obstructive pulmonary disease candidate gene associations.

Case-control studies have successfully identified many significant genetic associations for complex diseases, but lack of replication has been a criticism of case-control genetic association studies in general. We selected 12 candidate genes with reported associations to chronic obstructive pulmonary disease (COPD) and genotyped 29 polymorphisms in a family-based study and in a case-control study. In the Boston Early-Onset COPD Study families, significant associations with quantitative and/or qualitative COPD-related phenotypes were found for the tumor necrosis factor (TNF)-alpha -308G>A promoter polymorphism (P < 0.02), a coding variant in surfactant protein B (SFTPB Thr131Ile) (P = 0.03), and the (GT)(31) allele of the heme oxygenase (HMOX1) promoter short tandem repeat (P = 0.02). In the case-control study, the SFTPB Thr131Ile polymorphism was associated with COPD, but only in the presence of a gene-by-environment interaction term (P = 0.01 for both main effect and interaction). The 30-repeat, but not the 31-repeat, allele of HMOX1 was associated (P = 0.04). The TNF -308G>A polymorphism was not significant. In addition, the microsomal epoxide hydrolase "fast" allele (EPHX1 His139Arg) was significantly associated in the case-control study (P = 0.03). Although some evidence for replication was found for SFTPB and HMOX1, none of the previously published COPD genetic associations was convincingly replicated across both study designs.

Adult↗

PubMed2005

Variation in total and specific IgE: effects of ethnicity and socioeconomic status.

BACKGROUND: Asthma is common in minority and disadvantaged populations, whereas atopic disorders other than asthma appear to be less prevalent. It is unclear whether the same holds true for objective markers of sensitization. OBJECTIVE: To determine the association of asthma, atopic disorders, and specific sensitization with race and socioeconomic factors. METHODS: We analyzed total and specific IgE among 882 women (577 white, 169 black, and 136 Hispanic) who delivered a child at a large tertiary hospital in Boston, Mass, and who were screened for participation in a family and birth cohort study. Race/ethnicity and other characteristics were obtained from screening questionnaires. Addresses were geocoded, and 3 census-based geographic area socioeconomic variables were derived from block group information from the 1990 US Census. RESULTS: Black and Hispanic women were more likely to come from areas with low socioeconomic indicators and were more likely to have asthma than white women. However, these women were less likely to have hay fever and eczema than their white counterparts. Compared with white women, black women had higher mean total IgE levels; had greater proportions of sensitization to indoor, outdoor, and fungal allergens; and were more than twice as likely to be sensitized to > or =3 aeroallergens. CONCLUSION: The racial/ethnic disparities in atopic disorders may represent either underdiagnosis or underreporting and suggest that allergy testing may be underused in some populations. Differences in total IgE levels and specific allergen sensitization are likely a result of the complex interplay between exposures associated with socioeconomic disadvantage.

Adult↗