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

被引:21
作者
Donfack, J
Kogut, P
Forsythe, S
Solway, J
Ober, C
机构
[1] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Med, Chicago, IL 60637 USA
关键词
asthma; atopy; muscarinic receptors;
D O I
10.1067/mai.2003.71
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
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 M-3 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: chi(2) = 38.55, P =.013). Conclusions: These results suggest a possible role for this gene in atopic disorders. (J Allergy Clin Immunol 2003;111:527-32.).
引用
收藏
页码:527 / 532
页数:6
相关论文
共 35 条
[1]   MODULATION OF NEUROTRANSMISSION IN AIRWAYS [J].
BARNES, PJ .
PHYSIOLOGICAL REVIEWS, 1992, 72 (03) :699-729
[2]   IDENTIFICATION OF A FAMILY OF MUSCARINIC ACETYLCHOLINE-RECEPTOR GENES [J].
BONNER, TI ;
BUCKLEY, NJ ;
YOUNG, AC ;
BRANN, MR .
SCIENCE, 1987, 237 (4814) :527-532
[3]  
BONNER TI, 1991, CYTOGENET CELL GENET, V58, P1850
[4]   SYMPATHETIC VERSUS PARASYMPATHETIC NERVOUS REGULATION OF AIRWAYS IN DOGS [J].
CABEZAS, GA ;
GRAF, PD ;
NADEL, JA .
JOURNAL OF APPLIED PHYSIOLOGY, 1971, 31 (05) :651-+
[5]   EFFECT OF VAGOTOMY AND VAGAL STIMULATION ON LUNG MECHANICS AND CIRCULATION [J].
COLEBATCH, HJH ;
HALMAGYI, DF .
JOURNAL OF APPLIED PHYSIOLOGY, 1963, 18 (05) :881-&
[6]   A genome-wide search for quantitative trait loci underlying asthma [J].
Daniels, SE ;
Bhattacharrya, S ;
James, A ;
Leaves, NI ;
Young, A ;
Hill, MR ;
Faux, JA ;
Ryan, GF ;
leSouef, PN ;
Lathrop, GM ;
Musk, AW ;
Cookson, WOCM .
NATURE, 1996, 383 (6597) :247-250
[7]   The glutamine 27 beta(2)-adrenoceptor polymorphism is associated with elevated IgE levels in asthmatic families [J].
Dewar, JC ;
Wilkinson, J ;
Wheatley, A ;
Thomas, NS ;
Doull, I ;
Morton, N ;
Lio, P ;
Harvey, JF ;
Liggett, SB ;
Holgate, ST ;
Hall, IP .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1997, 100 (02) :261-265
[8]   EFFECT OF AN INHALED ATROPINE-LIKE AGENT ON NORMAL AIRWAY FUNCTION [J].
DOUGLAS, NJ ;
SUDLOW, MF ;
FLENLEY, DC .
JOURNAL OF APPLIED PHYSIOLOGY, 1979, 46 (02) :256-262
[9]   Mutation screening of the muscarinic M2 and M3 receptor genes in normal and asthmatic subjects [J].
Fenech, AG ;
Ebejer, MJ ;
Felice, AE ;
Ellul-Micallef, R ;
Hall, IP .
BRITISH JOURNAL OF PHARMACOLOGY, 2001, 133 (01) :43-48
[10]   Structure and transcription of the human m3 muscarinic receptor gene [J].
Forsythe, SM ;
Kogut, PC ;
McConville, JF ;
Fu, YP ;
McCauley, JA ;
Halayko, AJ ;
Liu, HW ;
Kao, A ;
Fernandes, DJ ;
Bellam, S ;
Fuchs, E ;
Sinha, S ;
Bell, GI ;
Camoretti-Mercado, B ;
Solway, J .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2002, 26 (03) :298-305