Gene encoding Duffy antigen/receptor for chemokines is associated with asthma and IgE in three populations.

RATIONALE: Asthma prevalence and severity are high among underserved minorities, including those of African descent. The Duffy antigen/receptor for chemokines is the receptor for Plasmodium vivax on erythrocytes and functions as a chemokine-clearing receptor. Unlike European populations, decreased expression of the receptor on erythrocytes is common among populations of African descent, and results from a functional T-46C polymorphism (rs2814778) in the promoter. This variant provides an evolutionary advantage in malaria-endemic regions, because Duffy antigen/receptor for chemokines-negative erythrocytes are more resistant to infection by P. vivax. OBJECTIVES: To determine the role of the rs2814778 polymorphism in asthma and atopy as measured by total serum IgE levels among four populations of African descent (African Caribbean, African American, Brazilian, and Colombian) and a European American population. METHODS: Family-based association tests were performed in each of the five populations to test for association between the rs2814778 polymorphism and asthma or total IgE concentration. MEASUREMENTS AND MAIN RESULTS: Asthma was significantly associated with the rs2814778 polymorphism in the African Caribbean, Colombian, and Brazilian families (P < 0.05). High total IgE levels were associated with this variant in African Caribbean and Colombian families (P < 0.05). The variant allele was not polymorphic among European Americans. CONCLUSIONS: Susceptibility to asthma and atopy among certain populations of African descent is influenced by a functional polymorphism in the gene encoding Duffy antigen/receptor for chemokines. This genetic variant, which confers resistance to malarial parasitic infection, may also partially explain ethnic differences in morbidity of asthma.

Integrating Parenting Support Within and Beyond the Pediatric Medical Home.

Positive parenting programs, developmental support services, and evidence-based home visiting programs can effectively provide parenting support and improve health and developmental outcomes for at-risk children. Few models, however, have integrated referrals for on-site support and home visiting programs into the provision of routine pediatric care within a medical home. This article describes an innovative approach, through partnership with a community-based organization, to deliver on-site and home visiting support services for children and families within and beyond the medical home. Our model offers a system of on-site services, including parenting, behavior, and/or development support, with optional intensive home visiting services. Assessment included description of the population served, delineation of services provided, and qualitative identification of key themes of the impact of services, illustrated by case examples. This replicable model describes untapped potential of the pediatric medical home as a springboard to mitigate risk and optimize children's health and development.

Comparison of SNP tagging methods using empirical data: association study of 713 SNPs on chromosome 12q14.3-12q24.21 for asthma and total serum IgE in an African Caribbean population.

Few comparison studies have been performed on single nucleotide polymorphism (SNP) tagging methods to examine their consistency and effectiveness in terms of inferences about association with disease. We applied several SNP tagging methods to SNPs on chromosome 12q (n=713) and compared the utility of these methods to detect association for asthma and serum IgE levels among a sample of African Caribbean families from Barbados selected through asthmatic probands. We found that a high level of information regarding association is retained in Clayton's htSNP, Stram's TagSNP, and de Bakker's Tagger. We also found a high degree of consistency between TagSNP and Tagger. Using this set of 713 SNPs on chromosome 12q, our study provides insight towards analytic strategies for future studies of complex traits.

Polymorphisms in the novel gene acyloxyacyl hydroxylase (AOAH) are associated with asthma and associated phenotypes.

BACKGROUND: The gene encoding acyloxyacyl hydroxylase (AOAH), an enzyme that hydrolyzes secondary fatty acyl chains of LPS, is localized on chromosome 7p14-p12, where evidence for linkage to total IgE (tIgE) concentrations and asthma has been previously reported. OBJECTIVE: We hypothesized that variants in AOAH are associated with asthma and related phenotypes. Because both AOAH and soluble CD14 respond to LPS, we tested for gene-gene interaction. METHODS: We investigated the association between 28 single nucleotide polymorphisms throughout the AOAH gene and asthma, concentrations of tIgE, the ratio of IL-13/IFN-gamma, and soluble CD14 levels among 125 African Caribbean, multiplex asthmatic pedigrees (n = 834). Real-time PCR was used to assess whether AOAH cDNA expression differed with AOAH genotype. RESULTS: Significant effects were observed for all 4 phenotypes and AOAH markers in 3 distinct regions (promoter, introns 1-6, and the intron 12/exon 13 boundary/intron 13 region) by means of single-marker and haplotype analyses, with the strongest evidence for a 2-single-nucleotide-polymorphism haplotype and log[tIgE] (P = .006). There was no difference in AOAH expression levels by AOAH genotype for any of the markers. Comparing genotypic distributions at both the AOAH marker rs2727831 and CD14(-260)C >T raises the possibility of gene-gene interaction (P = .006-.036). CONCLUSION: Our results indicate that polymorphisms in markers within the AOAH gene are associated with risk of asthma and associated quantitative traits (IgE and cytokine levels) among asthmatic subjects and their families in Barbados, and there is an interactive effect on tIgE and asthma concentrations between an AOAH marker and the functional CD14(-260)C >T polymorphism. CLINICAL IMPLICATIONS: AOAH is a novel innate immunity candidate gene associated with asthma and related phenotypes in an African ancestry population.

Inheritance of total serum IgE in the isolated Tangier Island population from Virginia: complexities associated with genealogical depth of pedigrees in segregation analyses.

OBJECTIVES: This study was aimed at performing a segregation analysis of total serum immunoglobulin E (tIgE) in an isolated population using maximal genealogical information permitted by current software and computer capacities, while assessing the reliability of the best-fitting model of inheritance for tIgE through simulations. METHODS: All current Tangier Island, VA, residents (n = 664) belonged to one large extended pedigree (n = 3,501) spanning 13 generations, with an average inbreeding coefficient of 0.009. Phenotype data were obtained on 453 (68.2%) of the residents using a population-based recruitment scheme. Due to computational limitations resulting from the extremely complex pedigree structure, analysis on only two pedigree reconstructions was feasible: a reduced pedigree retaining all phenotyped individuals and their parents as 57 distinct families, and 922 nuclear families. RESULTS: Familial correlations and heritability calculations reveal a significant genetic component to tIgE in these data (heritability = 26%). The most parsimonious model to explain tIgE distribution indicated by the reduced pedigree structure was a two-distribution Mendelian model. However, larger and non-genetic models could not be rejected. Simulations over 200 replicates performed to evaluate the reliability of this model, indicated that using restricted genealogical information had minimal impact on results of segregation analyses performed here.

Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study.

BACKGROUND: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. OBJECTIVE: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. METHODS: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. RESULTS: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma ( z = -2.444; P = .015) and asthma severity ( z = -2.615; P = .009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores ( P < .002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. CONCLUSION: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.