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1.  Placental transfer and concentrations of cadmium, mercury, lead, and selenium in mothers, newborns, and young children 
There is an emerging hypothesis that exposure to cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in utero and early childhood could have long-term health consequences. However, there are sparse data on early life exposures to these elements in US populations, particularly in urban minority samples. This study measured levels of Cd, Hg, Pb, and Se in 50 paired maternal, umbilical cord, and postnatal blood samples from the Boston Birth Cohort (BBC). Maternal exposure to Cd, Hg, Pb, and Se was 100% detectable in red blood cells (RBCs), and there was a high degree of maternal–fetal transfer of Hg, Pb, and Se. In particular, we found that Hg levels in cord RBCs were 1.5 times higher than those found in the mothers. This study also investigated changes in concentrations of Cd, Hg, Pb, and Se during the first few years of life. We found decreased levels of Hg and Se but elevated Pb levels in early childhood. Finally, this study investigated the association between metal burden and preterm birth and low birthweight. We found significantly higher levels of Hg in maternal and cord plasma and RBCs in preterm or low birthweight births, compared with term or normal birthweight births. In conclusion, this study showed that maternal exposure to these elements was widespread in the BBC, and maternal–fetal transfer was a major source of early life exposure to Hg, Pb, and Se. Our results also suggest that RBCs are better than plasma at reflecting the trans-placental transfer of Hg, Pb, and Se from the mother to the fetus. Our study findings remain to be confirmed in larger studies, and the implications for early screening and interventions of preconception and pregnant mothers and newborns warrant further investigation.
PMCID: PMC4329243  PMID: 24756102
cadmium (Cd); mercury (Hg); lead (Pb) and selenium (Se); maternal–fetal transfer; early life exposure
2.  Genetic determinants in the development of sensitization to environmental allergens in early childhood 
Sensitization to environmental allergens remains one of the strongest risk factors for asthma, and there is likely a genetic basis. We sought to identify genetic determinants for the development of allergic sensitization to environmental allergens, particularly cockroach allergen, in early childhood. A total of 631 children with the information about genotypic data on 895 single nucleotide polymorphisms (SNPs) in 179 candidate genes were selected from an existing dataset (Boston Birth Cohort). Genetic analysis was performed for allergic sensitizations among all subjects and sub-population, Black/African, respectively. Eight SNPs in seven genes showed significant association with allergic sensitization with P < 0.05, including two top SNPs, rs7851969 in JAK2 (P = 0.003) and rs11739089 in CNOT6 (P = 0.008). When analyses were specifically performed for cockroach sensitization, 16 SNPs in 13 genes showed P < 0.05, including five genes with SNPs at P < 0.01 (JAK1, JAK3, IL5RA, FCER1A, and ADAM33). Particularly, haplotype analyses demonstrated that multiple-haplotypes in FCER1A were significantly associated with cockroach sensitization with the strongest association for a 2-marker haplotype (rs6665683T-rs12136904T, P = 0.001). Furthermore, SNP rs6665683 was marginally associated with the levels of cockroach allergen specific IgE. When a similar analysis was performed for house dust mite, four SNPs in three genes (JAK2, MAML1, and NOD1) had P < 0.01. Of these, JAK2 appeared to be an only gene showing association across the sensitizations we analyzed. Some of findings were further validated when analysis was limited to black population. Our study identified several loci that may confer the susceptibility to allergic sensitization, and suggested that sensitization to allergens may depend on their unique loci.
PMCID: PMC4257764  PMID: 25505553
Asthma; allergic sensitization; cockroach sensitization; house dust mites; single nucleotide polymorphisms
3.  IgE but not IgG4 Antibodies to Ara h 2 Distinguish Peanut Allergy from Asymptomatic Peanut Sensitization 
Allergy  2012;67(12):1538-1546.
There are no available clinical tests that can accurately predict peanut allergy (PA) and/or anaphylaxis. This study is aimed at evaluating whether the component-resolved diagnostic (CRD) IgE and IgG4 tests can 1) distinguish PA from asymptomatic peanut sensitization; and 2) differentiate anaphylactic vs. non-anaphylactic PA.
This study included 20 non-atopic controls, 58 asymptomatically peanut-sensitized children, 55 non-anaphylactic and 53 anaphylactic PA cases from the Chicago Food Allergy Study. IgE and IgG4 to 103 allergens were measured using the ImmunoCAP ISAC technology, and were compared among each group of children. The random forest test was applied to estimate each allergen’s ability to predict PA and/or peanut anaphylaxis.
PA cases (with or without anaphylaxis) had significantly higher IgE reactivity to Ara h 1–3 (peanut allergens) and Gly m 5–6 (soy allergens) than asymptomatically-sensitized children (p<0.00001). Similar but more modest relationships were found for IgG4 to Ara h 2 (p<0.01). IgE to Ara h 2 was the major contributor to accurate discrimination between PA and asymptomatic sensitization. With an optimal cutoff point of 0.65 ISU-E, it conferred 99.1% sensitivity, 98.3% specificity, and a 1.2% misclassification rate in the prediction of PA, which represented a higher discriminative accuracy than IgE to whole peanut extract (p=0.008). However, none of the IgE and/or IgG4 tests could significantly differentiate peanut anaphylaxis from non-anaphylactic PA.
IgE to Ara h 2 can efficiently differentiate clinical PA from asymptomatic peanut sensitization, which may represent a major step forward in the diagnosis of PA.
PMCID: PMC3499645  PMID: 23094689
Ara h 2; Component-resolved diagnostics; Diagnostic performance; Peanut allergy; Peanut anaphylaxis
4.  Gene Polymorphisms, Breastfeeding and Development of Food Sensitization in Early Childhood 
The impact of breastfeeding on the development of allergic disease is uncertain. There are no data that show whether this relationship varies by individual genotypes.
To evaluate the effect of breastfeeding and gene-breastfeeding interactions on food sensitization (FS) in a prospective U.S. birth cohort.
This study included 970 children who were prospectively followed since birth. Breastfeeding history was obtained from a standardized questionnaire interview. FS was defined as specific IgE ≥0.35 kUA/L to any of eight common food allergens. Eighty-eight potentially functional SNPs were genotyped from 18 genes involved in innate immunity or TH1/TH2 balance. Logistic regression models were used to test the effects of breastfeeding and gene-breastfeeding interactions on FS, with adjustment for pertinent covariates.
Children who were ever breastfed (n=739), including exclusively breastfed children, were at a 1.5 (95%CI=1.1-2.1, p=0.019) times higher risk of FS than never breastfed children (n=231). This association was significantly modified by rs425648 in the IL12RB1gene (pinteraction=0.0007): breastfeeding increased the risk of FS (OR=2.0, 95%CI=1.4-3.1, p= 0.0005) in children carrying the GG genotype but decreased the risk (OR=0.6, 95%CI=0.3-1.4, p=0.252) in children carrying the GT/TT genotype. Similar interactions were observed for SNPs in the TLR9 (rs352140) and TSLP (rs3806933) genes. The interaction between the combined genotypes of the three SNPs and breastfeeding on FS was even stronger (pinteraction<10-5).
Our data suggest that the effect of breastfeeding on FS was modified by SNPs in the IL12RB1, TLR9, and TSLP genes both individually and jointly. Our findings underscore the importance of considering individual genetic variations in assessing this relationship.
PMCID: PMC3149737  PMID: 21689850
Breastfeeding; food sensitization; gene-environment interaction
5.  Early Life Eczema, Food Introduction, and Risk of Food Allergy in Children 
The effect of food introduction timing on the development of food allergy remains controversial. We sought to examine whether the presence of childhood eczema changes the relationship between timing of food introduction and food allergy. The analysis includes 960 children recruited as part of a family-based food allergy cohort. Food allergy was determined by objective symptoms developing within 2 hours of ingestion, corroborated by skin prick testing/specific IgE. Physician diagnosis of eczema and timing of formula and solid food introduction were obtained by standardized interview. Cox Regression analysis provided hazard ratios for the development of food allergy for the same subgroups. Logistic regression models estimated the association of eczema and formula/food introduction with the risk of food allergy, individually and jointly. Of the 960 children, 411 (42.8%) were allergic to 1 or more foods and 391 (40.7%) had eczema. Children with eczema had a 8.4-fold higher risk of food allergy (OR, 95% CI: 8.4, 5.9–12.1). Among all children, later (>6 months) formula and rice/wheat cereal introduction lowered the risk of food allergy. In joint analysis, children without eczema who had later formula (OR, 95% CI: 0.5, 0.3–0.9) and later (>1 year) solid food (OR, 95% CI: 0.5, 0.3–0.95) introduction had a lower risk of food allergy. Among children with eczema, timing of food or formula introduction did not modify the risk of developing food allergy. Later food introduction was protective for food allergy in children without eczema but did not alter the risk of developing food allergy in children with eczema.
PMCID: PMC3281290  PMID: 22375277
6.  Familial Aggregation of Food Allergy and Sensitization to Food Allergens: A Family-Based Study 
The increasing prevalence of food allergy (FA) is a growing clinical and public health problem. The contribution of genetic factors to FA remains largely unknown.
This study examined the pattern of familial aggregation and the degree to which genetic factors contribute to FA and sensitization to food allergens.
This study included 581 nuclear families (2,004 subjects) as part of an ongoing FA study in Chicago, IL, USA. FA was defined by a set of criteria including timing, clinical symptoms obtained via standardized questionnaire interview, and corroborative specific IgE cutoffs for >=95% positive predictive value (PPV) for food allergens measured by Phadia ImmunoCAP. Familial aggregation of FA as well as sensitization to food allergens were examined using generalized estimating equation (GEE) models, with adjustment for important covariates including age, gender, ethnicity and birth order. Heritability was estimated for food-specific IgE measurements.
FA in the index child was a significant and independent predictor of FA in other siblings (OR=2.6, 95%CI:1.2–5.6, p=0.01). There were significant and positive associations among family members (father-offspring, mother-offspring, index-other siblings) for total IgE and specific IgE to all the 9 major food allergens tested in this sample (sesame, peanut, wheat, milk, egg white, soy, walnut, shrimp and cod fish). The estimated heritability of food-specific IgE ranged from 0.15 to 0.35 and was statistically significant for all the 9 tested food allergens.
This family-based study demonstrates strong familial aggregation of food allergy and sensitization to food allergens, especially, among siblings. The heritability estimates indicate that food-specific IgE is likely influenced by both genetic and environmental factors. Together, this study provides strong evidence that both host genetic susceptibilityand environmental factors determine the complex trait of IgE-mediated food allergy.
PMCID: PMC2729087  PMID: 19016802
familial aggregation; heritability; food allergy; sensitization to food allergens; IgE-mediated
7.  Dissociation between the Prevalence of Atopy and Allergic Disease in Rural China among Children and Adults 
The prevalence of allergic diseases is increasing worldwide, but the reasons are not well understood. Previous studies suggest that this trend may be associated with lifestyle and urbanization.
To describe patterns of sensitization and allergic disease in an unselected agricultural Chinese population.
The data was derived from a community-based twin study in Anqing, China. Skin prick testing was performed to foods and aeroallergens. Atopy was defined as sensitization to ≥1 allergen. Allergic disease was ascertained by self-report. The analysis was stratified by sex and age (children [11-17 years] and adults [≥18 years]) and included 1059 same-sex twin pairs.
Of 2118 subjects, 57.6% were male (n=1220). Ages ranged from 11-71 years; 43.3% were children (n=918). Atopy was observed in 47.2% (n=999) of participants. The most common sensitizing foods were shellfish (16.7%) and peanut (12.3%). The most common sensitizing aeroallergens were dust mite (30.6%) and cockroach (25.2%). Birth order and zygosity had no effect on sensitization rates. Multivariate logistic regression models revealed risk factors for sensitization include age for foods and sex for aeroallergens. The rates of food allergy and asthma were estimated to be <1%.
Atopic sensitization was common in this rural farming Chinese population, particularly to shellfish, peanut, dust mite, and cockroach. The prevalence of allergic disease, in contrast, was quite low.
Clinical Implications
Allergen sensitization was far more common than the rate of self-reported allergic disease in this community. Evidence of sensitization is an inadequate marker of allergic disease and better correlates with clinical disease are needed.
Capsule summary
Among this large unselected Chinese rural farming community, atopy was observed in nearly half of the study subjects, but the rate of allergic disease was comparatively very low.
PMCID: PMC2747487  PMID: 18805578
aeroallergens; rural; farming community; Chinese; food allergens; prevalence; sensitization; skin prick tests

Results 1-7 (7)