State of the science: Allergy and asthma genetics

In our August News Beyond Our Pages section, we covered the consensus of the NHLBI Lung Division workshop on future directions of genomic research. This month, Deborah Meyers, PhD, co-director of the Center for Human Genomics and Personalized Medicine at Wake Forest University, presents a concise overview of what we know about the genetics of asthma and allergy.

Focusing on results from genome-wide association studies (GWAS), she discusses 5 pivotal research areas: phenotypic diversity, genetic susceptibility influence on disease expression, racial genotyping, the role of normal lung function variation in asthma, and influences of other inflammatory diseases on asthma and allergy.

Dr. Meyers comments that phenotypic heterogeneity seen in asthma will require genetic characterization to realize new approaches to prevention and management. She points out that this same phenotypic heterogeneity may explain why GWAS often identify different sets of genes across different asthma populations. She discusses the need to characterize racial genetic variation, especially in light of recent research that demonstrated that an alternate allele was critical for asthma susceptibility in African Americans in contrast to the relevant allele identified in the white population. Further, she discusses the need to correlate normal lung function variation and epigenetic influence on asthma/allergy disease susceptibility and severity.

Dr. Meyers notes that DNA susceptibility testing is already available. She states, however, that susceptibility testing will probably not pan out to be useful as a diagnostic tool. Dr. Meyers concludes with the comment that systems biology will provide necessary rigor to synthesize the great volume of data into cogent, useful disease profiles.

Do you have any questions for the authors, or comments about this study? We want to hear from you. Please feel free to post your own questions or comments. All questions and comments will be forwarded to the authors for a response.

Spectroscopy mirrors AD genotypes

Mutations in the filaggrin gene family are known to be associated with atopic dermatitis (AD). Filaggrin (FLG) is a critical component of the epidermal differentiation complex and its degradation products accumulate in the stratum corneum (SC) layer with hygroscopic amino acids to produce natural moisturizing factor (NMF), which is lost via transepidermal water depletion in AD patients. In this issue, O’Regan and co-authors propose that the filaggrin-associated AD genotype could be detected by Raman spectroscopy of the NMF content of the SC and that the NMF content could serve to separate FLG-associated AD from non-FLG-associated AD. Further, they examine the correlation of FLG-associated AD to transepidermal water loss (TEWL) and palmar hyperlinearity.

O’Regan and colleagues generate depth profiles of NMF content from AD study subjects and compare the profiles to Raman spectra for normal SC. Reference spectra profiles include tyrosine, which is known to be elevated in FLG-associated AD. They find that NMF content spectra can distinguish not only FLG-associated AD from non-FLG-associated AD, but also minor allele heterozygosity. Additionally, tyrosine content is significantly associated with the homozygous FLG genotype, suggesting a possible clinical biomarker. O’Regan et al. also report significant relationship between the clinical finding of palmar hyperlinearity, NMF content and filaggrin genotype.

Finally, the authors find that TEWL in moderate to severe AD is independent of filaggrin genotype, suggesting that TEWL results from other AD immunopathology.

Do you have any questions for the authors, or comments about this study? We want to hear from you. Please feel free to post your own questions or comments. All questions and comments will be forwarded to the authors for a response.