title: Polymorphisms in the muscarinic receptor 1 gene confer susceptibility to asthma in Japanese subjects.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: First Department of Medicine, Hokkaido University Graduate School of Medicine, N-15 W-7, Kita-Ku, Sapporo 060-8638, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Maeda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
authors.forename: Eisei
authors.initials: E
authors.lastname: Jinushi
authors.forename: Ayumi
authors.initials: A
authors.lastname: Honda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Takahashi
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Fukui
authors.forename: Satoshi
authors.initials: S
authors.lastname: Konno
authors.forename: Tadamichi
authors.initials: T
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
authors.forename: Etsuro
authors.initials: E
authors.lastname: Yamaguchi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043643:Receptor, Muscarinic M1 / Q000235:genetics*; D011976:Receptors, Muscarinic / Q000235:genetics*
chemical_list: C086088:CHRM1 protein, human; D043643:Receptor, Muscarinic M1; D011976:Receptors, Muscarinic