Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma in Japanese subjects.

Authors: Maeda, Y  Hizawa, N  Jinushi, E  Honda, A  Takahashi, D  Fukui, Y  Konno, S  Shimizu, T  Shimizu, H  Yamaguchi, E  Nishimura, M 
Citation: Maeda Y, etal., Am J Respir Crit Care Med. 2006 Nov 15;174(10):1119-24. Epub 2006 Aug 24.
Pubmed: (View Article at PubMed) PMID:16931638
DOI: Full-text: DOI:10.1164/rccm.200601-081OC

RATIONALE: The human cholinergic receptor muscarinic-1 (CHRM1) is widely distributed in the lungs. In patients with asthma, CHRM1 may be involved in airway constriction, airway epithelial cell proliferation, and airway inflammation. The CHRM1 gene is located on chromosome 11q13, which is one of the candidate loci for asthma and atopy. OBJECTIVES: To determine the role of the CHRM1 gene polymorphisms in asthma. METHODS: We studied nine single-nucleotide polymorphisms (-18379G > A, -9697C > T, -6965T > C, -4953A > G, +267A > C, +1353C > T, +3970C > G, +5418C > G, and +5455G > T) in a case-control study using 326 patients with asthma and 333 healthy control subjects. We also examined functional consequences of the -9697C > T and -4953A > G polymorphisms at the regulatory region using an mRNA reporter assay. MEASUREMENTS AND MAIN RESULTS: Two common single-nucleotide polymorphisms (-9697C > T and -4953A > G) were associated with asthma. The odds ratio for the TT homozygotes at the -9697C > T polymorphism was 0.29 compared with the CC homozygotes (95% confidence interval, 0.12-0.73; p = 0.008), and the odds ratio for the GG homozygotes at the -4953A > G polymorphism was 1.86 compared with the AA homozygotes (95% confidence interval, 1.04-3.34; p = 0.038). Haplotype analysis showed that the -9697T/-6965T/-4953A haplotype was associated with a lower risk of asthma (p = 0.00055) and the -9697C/-6965T/-4953G haplotype was associated with an increased risk of asthma (p = 0.020). The -9697T/-4953A haplotype was also associated with lower luciferase activity in vitro compared with the -9697C/-4953G haplotype. CONCLUSIONS: This study, together with an in vitro functional study, suggests that the CHRM1 gene is an important susceptibility locus for asthma on chromosome11q13.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 5133416
Created: 2011-06-15
Species: All species
Last Modified: 2011-06-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.