Smoke exposure interacts with gene ADAM33 to increase asthma risk

ADAM33 is the first identified asthma gene by positional cloning (also known as ADAM metallopeptidase domain 33 or Adamalysin). ADAM stands for "A Disintegrin And Metalloprotease."

ADAM33 gene encodes a member of the ADAM (A Disintegrin And Metalloprotease domain) family - membrane-anchored peptidase proteins structurally related to snake venom disintegrins. ADAMs are classified as Sheddases because they cut off or shed extracellular portions of transmembrane proteins. For example, ADAM 10 can cut off part of the HER2 receptor, activating it. Sheddase inhibitors active on ADAM-10 and -17 can potentiate anti-cancer therapy.

Sheddases are membrane-bound enzymes that cleave extracellular portions of transmembrane proteins, releasing the soluble ectodomains from the cell surface.

ADAM33 is associated with early-life lung function and decline of forced expiratory volume in 1 s (FEV1).

In utero and postnatal cigarette smoke exposure (CSE) leads to:

- reduced lung function
- development of BHR and asthma

The study authors confirmed associations between ADAM33 and the development of asthma (BHR).

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.

References:
Smoke exposure interacts with ADAM33 polymorphisms in the development of lung function and hyperresponsiveness. Reijmerink NE, Kerkhof M, Koppelman GH, Gerritsen J, de Jongste JC, Smit HA, Brunekreef B, Postma DS. Allergy. 2009 Feb 19.
ADAM33, from PubMed and Wikipedia, the free encyclopedia.
Healthvalue: Sheddases and ADAMs.
Image source: ADAM metallopeptidase domain 33, Wikipedia, public domain.