Asthma is a complex chronic disease of the airway, with notable airflow obstruction, eosinophilic inflammation, bronchoconstriction, and mucus hypersecretion . Asthma and allergy (asthma/allergy) disproportionately burden ethnic minority children in the United States, African Americans in particular [2–4]. Asthmatic individuals of African ancestry have also been characterized with higher IgE levels, higher dependence on treatment, and experience more severe clinical symptoms compared to Whites . Socioeconomic and environmental factors likely contribute to this disparity, but biological influences may play a discerning role.
Evidence exists for genomic features contributing to asthma pathogenesis, which in part relates to innate immunological characteristics such as variation in host defense genes . As conveyed in Peden DB 2002, with rapid urbanization over the last few decades, some scientists believe that genes previously protecting humans from parasitic infection may now contribute to a 'misdirected' response to environmental agents . Individuals residing in lower socioeconomic urban environments may experience a higher burden of environmental risk factors for allergy or asthma. Thus, evaluating genetic susceptibility to asthma/allergy in such vulnerable populations can help to direct public health prevention and treatment efforts.
A variety of review papers describe genes associated with allergy/asthma [6–10]. Ober et al.  list genes associated with asthma or atopy in more than 10 studies. This study evaluated 8 of these genes (IL4, IL13, TNF-α, HLA-DRB1, HLA-DQB1, FCER1B/MS4A2, CD14, ADAM33) as well as 3 glutathione-s-transferase genes (GSTM1, GSTP1, and GSTT1) for association with asthma/allergy among urban-residing African Americans. We note some key aspects of the biological significance of the genes evaluated.
Many of these genes play roles in the Th2 response to antigens, airway reactivity, or non-specific modulation of inflammation . The Th2 response is more characteristic of asthma in children compared to adults [6, 11] and typically accompanied by elevated immunoglobulin E (IgE) response to allergen . Genes within the chromosome 5q cytokine cluster have demonstrated strong associations with asthma/allergy, most notably for IL4 and IL13 [2, 7, 13–17]. Associations with total serum IgE have also been observed, but with variable findings across ethnicity . Also located on chromosome 5, the C-159T single nucleotide polymorphism (SNP) within the cluster of differentiation (CD14) gene has been associated with asthma, asthma severity [16, 19], and total serum IgE [20, 21]. The CD14 cell surface receptor mediates host interactions with endotoxin , suggesting a role in response to environmental stress. Another gene encoding a proinflammatory cytokine is tumor necrosis factor alpha (TNF-α), which has been associated with eosinophilic inflammation during lower respiratory tract infection with respiratory syncytial virus (RSV) in children .
Relevant to airway reactivity, a disintegrin and metalloprotease 33 (ADAM33) is expressed in bronchial tissue and whole lung [23, 24]. ADAM33 SNPs have been associated with airway remodeling and bronchial hyper-responsiveness , but have varying associations with asthma/allergy and total serum IgE across ethnic populations [16, 23, 26].
Human Leukocyte Antigen (HLA) class II genes relate to non-specific modulation of inflammation. HLA-DRB1 and HLA-DQB1 SNPs and haplotypes have been associated with a higher risk of toluene diisocyanate-induced occupational asthma , total serum IgE in Iranian subjects , atopy in Northern Chinese , Dermatophagoides Spp.-sensitive asthma in Venuezuelan individuals , and asthma severity in Whites in the United States , suggesting a broad role for these genes in asthma pathogenesis across ethnic groups.
The high affinity multimeric surface receptor for IgE (Fcepsilon R1beta) is essential for IgE-mediated acute allergic response, and is thereby relevant for asthma pathogenesis . Altered transcription of FcepsilonRlbeta correlates to the MS4A2 membrane-spanning 4-domains, subfamily A, member 2 (MS4A2), also known as "Fc fragment of IgE, high affinity I, receptor for beta polypeptide (FCER1B)". MS4A2 SNPs and haplotypes have been associated with asthma in various populations [33–35].
Outside of the host immune response framework are the glutathione S-transferase (GST) genes, a superfamily of genes that catalyze the conjugation of reduced glutathione to electrophilic and hydrophobic compounds . The conjugation of glutathione is important for the metabolism or detoxification of therapeutic drugs, environmental toxins, and products of oxidative stress, relevant to asthma [37, 38]. A recent meta-analysis of GST genes and asthma phenotypes reported that GSTM1 and GSTT1 showed increased asthma risk associated with the null genotype but that heterogeneity across studies and publication bias was a major limitation . In this paper, we consider key asthma candidate genes for association with asthma and allergy phenotypes among African American children living in Detroit, Michigan.