Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population

Joubert, Bonnie R.; Reif, David M.; Edwards, Stephen W.; Leiner, Kevin; Hudgens, Edward; Egeghy, Peter; Gallagher, Jane; Hubal, Elaine Cohen

doi:10.1186/1471-2350-12-25

Cited by 25 publications

(16 citation statements)

References 63 publications

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“…Moreover, multiple genetic alterations have been found to be associated with asthma in this racial group. 10,20 Nonetheless, at this point it is not clear whether this finding is due to genetics or socioeconomic disparities or a combination of these factors. 20 …”

Section: Discussionmentioning

confidence: 99%

African American Patients with Chronic Rhinosinusitis Have a Distinct Phenotype of Polyposis Associated with Increased Asthma Hospitalization

Mahdavinia

Benhammuda

Codispoti

et al. 2016

The Journal of Allergy and Clinical Immunology: In Practice

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BACKGROUND Chronic rhinosinusitis (CRS) is a common inflammatory disease of the upper airways that is often categorized into subtypes including “with” and “without” nasal polyps. However, the influence of multiple important epidemiologic factors, including race, on CRS has not been investigated. OBJECTIVE The present study assessed various phenotypic characteristics of CRS in patients, living in the United States, with different racial backgrounds. METHODS We performed a large retrospective cohort study of patients with CRS treated at a large urban tertiary care referral center in Chicago. RESULTS African American (AA) patients with CRS living in Chicago were more likely to report hyposmia as a symptom of CRS. Furthermore, AA patients with CRS who failed medical therapy and required surgical intervention had a significantly higher frequency of nasal polyposis and aspirin-exacerbated respiratory disease, and a higher disease severity index on computed tomography imaging than did white patients with CRS. The increased polyposis in AAs was associated with increased hospitalization for asthma. There were no differences in the prevalence of atopy, asthma, atopic dermatitis, food allergy, duration of disease, or number of surgeries between different races. CONCLUSIONS AAs with refractory CRS are at increased risk for nasal polyposis, smell loss, aspirin-exacerbated respiratory disease, and a greater severity of disease based on imaging, resulting in increased health care utilization.

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Section: Discussionmentioning

confidence: 99%

African American Patients with Chronic Rhinosinusitis Have a Distinct Phenotype of Polyposis Associated with Increased Asthma Hospitalization

Mahdavinia

Benhammuda

Codispoti

et al. 2016

The Journal of Allergy and Clinical Immunology: In Practice

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“…18 However, there is evidence that asthma-associated loci make additive contributions to risk, recommending aggregating risk alleles. 19,20 Summing risk alleles across GWAS-identified SNPs to compute a “genetic risk score” (GRS) yields a quantitative index of genetic risk with a normal distribution 21 and a potentially larger effect size.…”

Section: Methodsmentioning

confidence: 99%

Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study

Belsky

Sears

Hancox

et al. 2013

The Lancet Respiratory Medicine

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BACKGROUND Genome-wide association studies (GWAS) have discovered loci that predispose to asthma. To integrate these new discoveries with emerging models of asthma pathobiology, research is needed to test how genetic discoveries relate to developmental and biological characteristics of asthma. METHODS We derived a multi-locus profile of genetic risk from published GWAS of asthma case status. We then tested associations between this “genetic risk score” and developmental and biological characteristics of asthma in a population-based long-running birth cohort, the Dunedin Longitudinal Study (n=1,037). We evaluated asthma onset, persistence, atopy, airway hyperresponsiveness, incompletely reversible airflow obstruction, and asthma-related school and work absenteeism and hospitalization during 9 prospective assessments spanning ages 9–38 years, when 95% of surviving cohort members were seen. INTERPRETATION Cohort members at higher genetic risk experienced asthma onset earlier in life (HR=1.12 [1.01–1.26]). Childhood-onset asthma cases at higher genetic risk were more likely to become life-course-persistent asthma cases (RR=1.36 [1.14–1.63]). Asthma cases at higher genetic risk more often manifested atopy (RR=1.07 [1.01–1.14]), airway hyperresponsiveness (RR=1.16 [1.03–1.32]), and incompletely reversible airflow obstruction (RR=1.28 [1.04–1.57]). They were also more likely to miss school or work due to asthma (IRR=1.38 [1.02–1.86]) and to be hospitalized with breathing problems (HR=1.38 [1.07–1.79]). Genotypic information about asthma risk was independent of and additive to information derived from cohort members’ family histories of asthma. CONCLUSIONS Findings from this population study confirm that GWAS-discoveries for asthma associate with a childhood-onset phenotype and advance asthma genetics beyond the original GWAS-discoveries in three ways: (1) We show that genetic risks predict which childhood-onset asthma cases remit and which become life-course-persistent cases, although these predictions are not sufficiently sensitive or specific to support immediate clinical translation; (2) We elucidate a biological profile of the asthma that arises from these genetic risks: asthma characterized by atopy and airway hyperresponsiveness and leading to incompletely reversible airflow obstruction; and (3) We describe the real-life impact of GWAS-discoveries by quantifying genetic associations with missed school and work and hospitalization.

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“…Two common deletion polymorphisms of GSTM1 and GSTT1 genes have been associated with asthma in children and adults [73–76]. In addition, a single nucleotide polymorphism in GSTM1 was also associated significantly with asthma in an African American urban population [77]. In this study, GSTM1 rs412543 C carriers were almost 3 times as likely to have asthma compared to individuals without the C allele.…”

Section: Association Of Gstm1 With Lung Inflammationmentioning

confidence: 56%

Role of GSTM1 in resistance to lung inflammation

Peden

Díaz-Sánchez

2012

Free Radical Biology and Medicine

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Lung inflammation resulting from oxidant/antioxidant imbalance is a common feature of many lung diseases. In particular, the role of enzymes regulated by the NF-E2-related factor 2 (Nrf2) transcription factor has recently received increased attention. Among these antioxidant genes, the glutathione S-transferase mu 1 (GSTM1) has been most extensively characterized since it has a null polymorphism which is highly prevalent in the population and associated with increased risk of inflammatory lung diseases. Present evidence suggests that GSTM1 acts through interactions with other genes and environmental factors, especially air pollutants. Here, we review GSTM1 gene expression and regulation and summarize the findings from epidemiological, clinical, animal and in vitro studies on the role played by GSTM1 in lung inflammation. We discuss limitations in the existing knowledge base and future perspectives and evaluate the potential of pharmacologic and genetic manipulation of the GSTM1 gene to modulate pulmonary inflammatory responses.

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Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population

Cited by 25 publications

References 63 publications

African American Patients with Chronic Rhinosinusitis Have a Distinct Phenotype of Polyposis Associated with Increased Asthma Hospitalization

African American Patients with Chronic Rhinosinusitis Have a Distinct Phenotype of Polyposis Associated with Increased Asthma Hospitalization

Polygenic risk and the development and course of asthma: an analysis of data from a four-decade longitudinal study

Role of GSTM1 in resistance to lung inflammation

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