β2-Adrenergic receptor promoter haplotype influences the severity of acute viral respiratory tract infection during infancy: a prospective cohort study
| Autor: | Paul E. Moore, Sara Reiss, Kimberly B. Woodward, Pingsheng Wu, Marshall L. Summar, Tina V. Hartert, Zhouwen Liu, Emma K. Larkin, Jessica Y. Islam, Kecia N. Carroll, Patricia A. Minton |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Genotype Biology Linkage Disequilibrium Statistics Nonparametric White People Cohort Studies 03 medical and health sciences 0302 clinical medicine Viral Respiratory Tract Infection Interquartile range 030225 pediatrics medicine Genetics Humans Genetics(clinical) Prospective Studies Prospective cohort study Promoter Regions Genetic Respiratory Tract Infections Genetics (clinical) Asthma Respiratory tract infections Haplotype Infant Newborn Odds ratio medicine.disease United States 3. Good health Black or African American 030228 respiratory system Haplotypes Bronchiolitis Immunology Female Receptors Adrenergic beta-2 Research Article |
| Zdroj: | BMC Medical Genetics |
| ISSN: | 1471-2350 |
| DOI: | 10.1186/s12881-015-0229-3 |
| Popis: | Background Despite the significant interest in β2-Adrenergic receptor (ADRB2) polymorphisms related to asthma, whether ADRB2 genetic variants are similarly associated with acute respiratory tract infections have not been studied. We hypothesized that genetic variants in ADRB2 associated with a response to asthma therapy during an asthma exacerbation were also associated with severity of acute respiratory tract infections. Methods To test this hypothesis, we genotyped 5 common polymorphisms in the promoter region and coding block of the ADRB2 gene (loci -2387, -2274, -1343, +46, and +79) from 374 Caucasian and African American term infants who were enrolled at the time of acute respiratory illness over four respiratory viral seasons. Severity of respiratory tract infections was measured using a bronchiolitis severity score (BSS; range = 0-12, clinically significant difference = 0.5) with a higher score indicating more severe disease. We assigned the promoter, coding and combined promoter and coding haplotypes to the unphased genotype data. The associations between each of these five single-nucleotide polymorphisms (SNPs) as well as the haplotypes and infant BSS were analyzed using nonparametric univariate analysis and multivariable proportional odds model separately in Caucasians and African Americans. Results There was no significant association between infant BSS and each of the SNPs in both Caucasians and African Americans. However, promoter haplotype CCA was associated with a decreased BSS in African Americans in a dose dependent manner. The median (interquartile range) BSS of infants with no copies of the CCA haplotype, one copy, and two copies of the CCA haplotype were 5.5 (2.0, 8.0), 4.0 (1.0, 7.5), and 3.0 (1.0, 4.0), respectively. This dose dependent relationship persisted after adjusting for infant age, gender, daycare exposure, secondhand smoke exposure, prior history of breastfeeding, siblings at home, and enrollment season (adjusted odds ratio: 0.59, 95 % confidence interval: 0.36, 0.98). There was no similar protective relationship of haplotype CCA on severity of respiratory tract infections identified in Caucasians. Conclusions ADRB2 genotype may be predictive of severity of acute respiratory tract infections in African Americans, and potentially identify a subset of infants who may respond to beta-agonist therapy. Electronic supplementary material The online version of this article (doi:10.1186/s12881-015-0229-3) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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