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

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 6 months 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.

Molecular mechanisms in atopic eczema: insights gained from genetic studies

“…To date, only one small WES study has been reported for eczema, in which exomes of 22 Ethiopian patients with ichthyosis vulgaris and atopic eczema were sequenced; this identified possible disease‐causing variants in FLG and related genes, as well as some novel candidate genes, in a rather heterogeneous pattern of risk . Exome sequencing data have been reported for FLG and related genes , and for the human leukocyte antigen region ; however, larger studies will be required to begin to systemically identify rare variants contributing to atopic eczema. In addition, whole genome sequencing and painstaking functional studies will be required to fully assess the complex contribution of non‐coding genetic variants, which is expected to be substantial .…”

Prenatal PM2.5 exposure and vitamin D–associated early persistent atopic dermatitis via placental methylation

“…54,55 In the Pediatric Eczema Elective Registry study, HLA-DRB1 was associated with increased prevalence and persistence of AD. 56 Although we report hypomethylation in AHRR, DPP10, and HLA-DRB1, the expected change in protein expression was limited to AHR associated with AHRR. Moreover, there is no overlap between differentially methylated genes and differentially expressed genes.…”

Association of atopic dermatitis with an increased risk of systemic lupus erythematosus

“…[ 7 12 ] In fact, individuals with certain human leukocyte antigen (HLA) genotypes, such as HLA-B and HLA-DRB1, are found to have an increased tendency to develop both diseases. [ 42 43 44 45 ] Nonetheless, common susceptibility locus and single nucleotide polymorphisms (SNPs) in HLA genes are yet to be found.…”