2 new asthma susceptibility genes: ORMDL3 and CHI3L1

Asthma is a disease of unknown etiology with underlying genetic factors. The specific genetic contributions to childhood asthma have been difficult to elucidate. Estimates of the heritability of asthma are as high as 70% (CCJM, 2012).

Human chromosomes (grey) capped by telomeres (white). Image source: Wikipedia, public domain.

Completion of the human genome sequence resulted in the identification of two new asthma susceptibility genes:


- CHI3L1

A common genetic variation at a locus controlling the expression of the ORMDL3 increases the susceptibility to asthma and is associated with poor asthma control in children and young adults.

SNPs associated with atopic diseases

Filaggrin gene
Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.

17q12-21 gene
ORMDL3 protein defects associated with asthma.

5q22-32 gene
CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.

3p21-22 gene
CCR5 is a chemokine receptor. SNP can be protective against asthma.

Xp22 gene
TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.

5q31 gene
IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.

ADRB2 gene
ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.

ADAM33 gene
Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.

GLCCI1 gene, rs37972 variant
A variant in the glucocorticoid-induced transcript 1 gene (GLCCI1), rs37972, associated with a decrease in forced expiratory volume in 1 second (FEV1) in response to treatment with inhaled glucocorticoids (NEJM, 09/2011).

IL6R and chromosome 11q13.5 have been identified as risk loci for asthma, and an IL6R antagonist (tocilizumab) may be effective therapy (Lancet, 2011).


Genes in asthma: new genes and new ways. Moffatt, Miriam F. Genetics and epidemiology, Current Opinion in Allergy & Clinical Immunology. 8(5):411-417, October 2008.
A polymorphism controlling ORMDL3 expression is associated with asthma that is poorly controlled by current medications. Tavendale R, Macgregor DF, Mukhopadhyay S, Palmer CN. J Allergy Clin Immunol. 2008 Apr;121(4):860-3.
PTGDR gene in asthma http://bit.ly/og1G7W
Consumer genomics company 23andMe now tests for hay fever, and atopic dermatitis. Clinical relevance is unclear.

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