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

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概要

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• 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.

• American Thoracic Society (ATS)の論文
• 2006-11-15

著者

• Nishimura M

  First Department Of Medicine Hokkaido University School Of Medicine

• Nakashima M

  Department Of Molecular Immunology And Clinical Immunology Medical Institute Of Bioregulation Kyushu

• TAKAHASHI Daisuke

  First Department of Medicine, Hokkaido University School of Medicine

• Takahashi Daisuke

  First Department Of Medicine Hokkaido University School Of Medicine

• Honda Ayumi

  Department Of Dermatology Graduate School Of Medicine University Of Toyama

• Maeda Yukiko

  First Department Of Medicine Hokkaido University School Of Medicine

• Shimizu Hiroshi

  Department Of Dermatology Hokkaido University Graduate School Of Medicine

• Shimizu Tadamichi

  Department Of Dermatology Toyama University School Of Medicine

• Shinoda Hiroyuki

  Faculty Of Pharmaceutical Sciences University Of Toyama

• Hizawa Nobuyuki

  Department Of Pulmonary Medicine Graduate School Of Comprehensive Human Sciences University Of Tsukuba

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