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


METHODS
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.
Donfack
Joseph
J
Department of Human Genetics, The University of Chicago, Chicago, Ill 60637, USA.
Kogut
Paul
P
Forsythe
Sean
S
Solway
Julian
J
Ober
Carole
C
D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000235:genetics*; D001483:Base Sequence / Q000235:genetics; D003058:Cockroaches / Q000276:immunology; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D006967:Hypersensitivity / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D010375:Pedigree; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic / Q000235:genetics*; D012016:Reference Values; D012882:Skin Tests; D020080:Tandem Repeat Sequences
D000485:Allergens; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic