Differences in Candidate Gene Association between European Ancestry and African American Asthmatic Children

Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, United States of America.
PLoS ONE (Impact Factor: 3.53). 02/2011; 6(2):e16522. DOI: 10.1371/journal.pone.0016522
Source: PubMed

ABSTRACT Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry.
Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls.
We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry.

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    ABSTRACT: This review explores the limitations of self-reported race, ethnicity, and genetic ancestry in biomedical research. Various terminologies are used to classify human differences in genomic research including race, ethnicity, and ancestry. Although race and ethnicity are related, race refers to a person¿s physical appearance, such as skin color and eye color. Ethnicity, on the other hand, refers to communality in cultural heritage, language, social practice, traditions, and geopolitical factors. Genetic ancestry inferred using ancestry informative markers (AIMs) is based on genetic/genomic data. Phenotype-based race/ethnicity information and data computed using AIMs often disagree. For example, self-reporting African Americans can have drastically different levels of African or European ancestry. Genetic analysis of individual ancestry shows that some self-identified African Americans have up to 99% of European ancestry, whereas some self-identified European Americans have substantial admixture from African ancestry. Similarly, African ancestry in the Latino population varies between 3% in Mexican Americans to 16% in Puerto Ricans. The implication of this is that, in African American or Latino populations, self-reported ancestry may not be as accurate as direct assessment of individual genomic information in predicting treatment outcomes. To better understand human genetic variation in the context of health disparities, we suggest using ¿ancestry¿ (or biogeographical ancestry) to describe actual genetic variation, ¿race¿ to describe health disparity in societies characterized by racial categories, and ¿ethnicity¿ to describe traditions, lifestyle, diet, and values. We also suggest using ancestry informative markers for precise characterization of individuals¿ biological ancestry. Understanding the sources of human genetic variation and the causes of health disparities could lead to interventions that would improve the health of all individuals.
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    ABSTRACT: IL4 -589C/T polymorphism has been implicated in susceptibility to pediatric asthma risk. Several studies investigated the association of this polymorphism with pediatric asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to assess the association between IL4 -589C/T polymorphism and pediatric asthma risk. Databases including Pubmed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and Wangfang were searched to find relevant studies. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. A significant association was found between IL4 -589C/T polymorphism and pediatric asthma risk (OR = 1.53, 95% CI 1.27-1.85). In the subgroup analyses by ethnicity, the significant association was found among Caucasians (OR = 1.70, 95 % CI 1.38-2.09) and Asians (OR = 1.58, 95 % CI 1.23-2.04). Our results suggested that IL4 -589C/T polymorphism conferred a risk factor of pediatric asthma.
    Inflammation 12/2014; DOI:10.1007/s10753-014-0086-9 · 1.92 Impact Factor

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