Sequence variation in the promoter region of the cholinergic receptor muscarinic 3 gene and asthma and atopy

J Allergy Clin Immunol. 2003 Mar;111(3):527-32. doi: 10.1067/mai.2003.71.

Abstract

Background: Muscarinic acetylcholine receptors are members of the superfamily of G protein-coupled, 7 transmembrane- spanning proteins. They are important in the development of airway hyperresponsiveness. In the lung the M3 receptor, encoded by the cholinergic receptor muscarinic 3 gene, is present in airway smooth muscle and mediates smooth muscle contraction.

Objective: We considered the cholinergic receptor muscarinic 3 gene as a possible candidate gene for bronchial asthma and initiated studies to identify polymorphisms in the promoter region.

Method: We identified 4 single-nucleotide polymorphisms (-708A/G, -627G/C, -513C/A, and -492C/T) and 2 short tandem repeat polymorphisms, a tetranucleotide (CTTT)12-20 and a dinucleotide (GT)6-19 repeat.

Results: None of the identified single nucleotide polymorphisms were significantly more frequent in asthmatic patients (n = 76) compared with in healthy control subjects (n = 81). Furthermore, there was no evidence for nonrandom transmission of short tandem repeat polymorphism haplotypes to individuals with asthma or bronchial hyperresponsiveness (P >.50) in a large Hutterite pedigree. However, there was significant nonrandom transmission of haplotypes to individuals with skin test reactivity to cockroach allergens (global transmission disequilibrium test: chi2 = 38.55, P =.013).

Conclusions: These results suggest a possible role for this gene in atopic disorders.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Allergens / immunology
  • Animals
  • Asthma / genetics*
  • Base Sequence / genetics
  • Cockroaches / immunology
  • Gene Frequency
  • Genetic Variation*
  • Haplotypes
  • Humans
  • Hypersensitivity / diagnosis
  • Hypersensitivity / genetics*
  • Hypersensitivity / immunology
  • Pedigree
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic / genetics*
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic / genetics*
  • Reference Values
  • Skin Tests
  • Tandem Repeat Sequences

Substances

  • Allergens
  • Receptor, Muscarinic M3
  • Receptors, Muscarinic