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Hum Immunol. 2015 Aug;76(8):571-7. doi: 10.1016/j.humimm.2015.08.003. Epub 2015 Aug 22.

Association of HLA-DRB1 genetic variants with the persistence of atopic dermatitis.

Author information

1
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States. Electronic address: margo@mail.med.upenn.edu.
2
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA, United States.
3
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States.
4
Division of Biostatistics and Epidemiology, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, TX, United States.
5
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Department of Dermatology, University of Pennsylvania, Philadelphia, PA, United States.
6
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States.
7
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Division of Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, United States; Abramson Cancer Center, Hospital of the University of Pennsylvania, Philadelphia, PA, United States.
8
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, United States.
9
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.
10
Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States; Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Abstract

Atopic dermatitis (AD) is a waxing and waning illness of childhood that is likely caused by interactions between an altered skin barrier and immune dysregulation. The goal of our study was to evaluate the association of DRB1 genetic variants and the persistence of AD using whole exome sequencing and high resolution typing. DRB1 was interrogated based on previous reports that utilized high throughput techniques. We evaluated an ongoing nation-wide long-term cohort of children with AD in which patients are asked every 6months about their medication use and their AD symptoms. In total, 87 African-American and 50 European-American children were evaluated. Genetic association analysis was performed using a software tool focusing on amino acid variable positions shared by HLA-DRB1 alleles covering the antigen presenting domain. Amino acid variations at position 9 (pocket 9), position 26, and position 78 (pocket 4) were marginally associated with the prevalence of AD. However, the odds ratio was 0.30 (0.14, 0.68; p=0.003) for residue 78, 0.27 (0.10, 0.69; p=0.006) for residue 26 and not significant for residue 9 with respect to the persistence of AD. In conclusion, amino acid variations at peptide-binding pockets of HLA-DRB1 were associated with the persistence of AD in African-American children.

KEYWORDS:

Atopic dermatitis; HLA alleles

PMID:
26307177
PMCID:
PMC4593755
DOI:
10.1016/j.humimm.2015.08.003
[Indexed for MEDLINE]
Free PMC Article

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