Article

African Ancestry is a Risk Factor for Asthma and High Total IgE Levels in African Admixed Populations

Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University (JHU), Baltimore, Maryland.
Genetic Epidemiology (Impact Factor: 2.6). 05/2013; 37(4). DOI: 10.1002/gepi.21702
Source: PubMed

ABSTRACT

Characterization of genetic admixture of populations in the Americas and the Caribbean is of interest for anthropological, epidemiological, and historical reasons. Asthma has a higher prevalence and is more severe in populations with a high African component. Association of African ancestry with asthma has been demonstrated. We estimated admixture proportions of samples from six trihybrid populations of African descent and determined the relationship between African ancestry and asthma and total serum IgE levels (tIgE). We genotyped 237 ancestry informative markers in asthmatics and nonasthmatic controls from Barbados (190/277), Jamaica (177/529), Brazil (40/220), Colombia (508/625), African Americans from New York (207/171), and African Americans from Baltimore/Washington, D.C. (625/757). We estimated individual ancestries and evaluated genetic stratification using Structure and principal component analysis. Association of African ancestry and asthma and tIgE was evaluated by regression analysis. Mean ± SD African ancestry ranged from 0.76 ± 0.10 among Barbadians to 0.33 ± 0.13 in Colombians. The European component varied from 0.14 ± 0.05 among Jamaicans and Barbadians to 0.26 ± 0.08 among Colombians. African ancestry was associated with risk for asthma in Colombians (odds ratio (OR) = 4.5, P = 0.001) Brazilians (OR = 136.5, P = 0.003), and African Americans of New York (OR: 4.7; P = 0.040). African ancestry was also associated with higher tIgE levels among Colombians (β = 1.3, P = 0.04), Barbadians (β = 3.8, P = 0.03), and Brazilians (β = 1.6, P = 0.03). Our findings indicate that African ancestry can account for, at least in part, the association between asthma and its associated trait, tIgE levels.

Download full-text

Full-text

Available from: Terri Beaty, Jul 29, 2014
  • Source
    • "The ancestral genetic background of Latin American populations (such as Colombia) has been shaped by recent and complex admixture processes between European, Native American and African populations (Bedoya et al., 2006; Rojas et al., 2010; Vergara et al., 2013; Wang et al., 2008). Such context is particularly interesting regarding the study of genetic epidemiology and the variation and distribution of alleles involved in susceptibility to complex diseases (Rojas et al., 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The wide variation in severity displayed during Dengue Virus (DENV) infection may be influenced by host susceptibility. In several epidemiological approaches, differences in disease outcomes have been found between some ethnic groups, suggesting that human genetic background has an important role in disease severity. In the Caribbean, It has been reported that populations of African descent present considerable less frequency of severe forms compared with Mestizo and White self-reported groups. Admixed populations offer advantages for genetic epidemiology studies due to variation and distribution of alleles, such as those involved in disease susceptibility, as well to provide explanations of individual variability in clinical outcomes. The current study analysed three Colombian populations, which like most of Latin American populations, are made up of the product of complex admixture processes between European, Native American and African ancestors; having as a main goal to assess the effect of genetic ancestry, estimated with 30 Ancestry Informative Markers (AIMs), on DENV infection severity. We found that African Ancestry has a protective effect against severe outcomes under several systems of clinical classification: Severe Dengue (OR: 0.963 for every 1% increase in African Ancestry, 95% confidence interval (0.934 - 0.993), p-value: 0.016), Dengue Haemorrhagic Fever (OR: 0.969, 95% CI (0.947 - 0.991), p-value: 0.006), and occurrence of haemorrhages (OR: 0.971, 95% CI (0.952 - 0.989), p-value: 0.002). Conversely, decrease from 100% to 0% African ancestry significantly increases the chance of severe outcomes: OR is 44-fold for Severe Dengue, 24-fold for Dengue Haemorrhagic Fever, and 20-fold for occurrence of haemorrhages. Furthermore, several warning signs also showed statistically significant association given more evidences in specific stages of DENV infection. These results provide consistent evidence in order to infer statistical models providing a framework for future genetic epidemiology and clinical studies.
    Full-text · Article · Oct 2014 · Infection Genetics and Evolution
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: life IgE responses in children living in the tropics: A prospective analysis. Pediatr Allergy Immunol 2013: 24: 788–797. Abstract Background: There are few birth cohort studies analyzing IgE sensitization in the tropics. Objectives: We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. Methods: Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1–S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. Results: Maternal total IgE (aOR: 2.43, 95% CI: 1.09–5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08–0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00–2.28, p = 0.05). Conclusions: In a socioeconomically deprived community from the tropics, sensitiza-tion to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing. The patterns and evolution of IgE antibody responses in early life provide important information about the natural history of atopy and allergic diseases. As the process is influenced by the environment and the genetic background of the population, birth cohort studies are valuable strategies to analyze early sensitization in humans. However, few of these investigations have been performed in the tropics (1–3), which is an important gap considering that about half of human beings live in this zone. The current concepts of diagnosis and management of allergic diseases are based on evidence collected in industrial-ized countries and temperate zones; then, knowledge of the evolution of IgE responses during infancy and its relationship
    Full-text · Article · Oct 2013
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are few birth cohort studies analyzing IgE sensitization in the tropics. We aimed to describe the evolution of total IgE and specific IgE responses to house-dust mite (HDM) allergens and Ascaris in a birth cohort (Risk Factors for Asthma and Allergy in the Tropics, FRAAT), analyzing their relationships with wheezing. Total and specific IgE were measured by ImmunoCap in mothers and children at four different time points (S1-S4) between 0 and 42 months. Parasite infection was evaluated by stool examination. Maternal total IgE (aOR: 2.43, 95% CI: 1.09-5.43; p = 0.03) and socio-demographic factors were associated with high cord blood (CB) total IgE. High CB total IgE was positively associated with higher Blomia tropicalis and Ascaris-specific IgE values during lifetime, but protected from recurrent wheezing (aOR: 0.26, 95% CI: 0.08-0.88, p = 0.03). Prevalence rates of IgE sensitization were high; at around 3 yr old, they were 33.3, 18.6, and 26.5% for B. tropicalis, Dermatophagoides pteronyssinus, and Ascaris, respectively. Indicators of unhygienic conditions were risk factors for HDM and Ascaris sensitization in children. A weak statistical association between B. tropicalis-specific IgE and ever wheezing was found (aOR: 1.47 95% CI: 1.00-2.28, p = 0.05). In a socioeconomically deprived community from the tropics, sensitization to HDM allergens was very frequent at early life, especially to B. tropicalis. In contrast to expected according to the hygiene hypothesis, unhygienic/poverty conditions were risk factors for allergen sensitization. High CB total IgE levels were a risk factor for allergen sensitization but protected from recurrent wheezing.
    Full-text · Article · Dec 2013 · Pediatric Allergy and Immunology
Show more