Publication date: Available online 4 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Michelle M. Stein, Emma E. Thompson, Nathan Schoettler, Britney A. Helling, Kevin M. Magnaye, Catherine Stanhope, Catherine Igartua, Andréanne Morin, Charles Washington, Dan Nicolae, Klaus Bønnelykke, Carole Ober
Chromosome 17q12-21 remains the most highly replicated and significant asthma locus. Genotypes in the core region defined by the first GWAS correlate with expression of two genes, ORMDL3 and GSDMB, making these prime candidate asthma genes, although recent studies have implicated GSDMA distal to and PGAP3 proximal to the core region as independent loci. We review here 10 years of studies on the 17q12-21 locus and suggest that genotype-specific risks for asthma at the proximal and distal loci are not specific to early onset asthma and mediated by PGAP3, ORMDL3, and/or GSDMA expression. We propose that the weak and inconsistent associations of 17q SNPs with asthma in African Americans is due to the high frequency of some 17q alleles, the breakdown of linkage disequilibrium on African-derived chromosomes, and possibly different early life asthma endotypes in these children. Finally, the inconsistent association between asthma and gene expression levels in blood or lung cells from older children and adults suggests that genotype effects may mediate asthma risk or protection during critical developmental windows and/or in response to relevant exposures in early life. Thus, studies of young children and ethnically diverse populations are required to fully understand the relationship between genotype and asthma phenotype and the gene regulatory architecture at this locus.
http://ift.tt/2m3liPh
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Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174
Παρασκευή 5 Ιανουαρίου 2018
A Decade of Research on the 17q12-21 Asthma Locus: Piecing Together the Puzzle
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