title: Linkage and association of childhood asthma with the chromosome 12 genes.
abstract: Several studies have shown linkage of chromosome region 12q13-24 to bronchial asthma and related phenotypes in ethnically diverse populations. In the Japanese population, a genome-wide study failed to show strong evidence of linkage of this region. Chromosome 12 genes that showed association with the disease in at least one report include: the signal transducer and activator of transcription 6 gene ( STAT6), the nitrogen oxide synthetase 1 gene ( NOS1), the interferon gamma gene ( IFNG), and the activation-induced cytidine deaminase gene ( AICDA). To evaluate the linkage between chromosome 12 and childhood asthma in the Japanese population, we performed sib-pair linkage analysis on childhood asthma families using 18 microsatellite markers on chromosome 12. To investigate association between chromosome 12 candidate genes and asthma, distributions of alleles and genotypes of repeat polymorphisms of STAT6, NOS1, and IFNG were compared between controls and patients. Single nucleotide polymorphism of AICDA was also investigated. Chromosome region 12q24.23-q24.33 showed suggestive linkage to asthma. The NOS1 intron 2 GT repeat and STAT6 exon 1 GT repeat were associated with asthma. Neither the IFNG intron 1 CA repeat nor 465C/T of AICDA showed any association with asthma. Our results suggest that NOS1 and STAT6 are asthma-susceptibility genes and that chromosome region 12q24.23-q24.33 contains other susceptibility gene(s).
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.|Department of Respiratory and Infectious Diseases, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. ysuzuki@mail.tains.tohoku.ac.jp.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Kamada
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kanno
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Tamari
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Xue
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Endo
authors.affiliation: Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Takayanagi
authors.affiliation: Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Japan.
authors.forename: Chifuyu
authors.initials: C
authors.lastname: Nakazawa
authors.affiliation: Morikawa Children's Clinic, Sendai, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Morikawa
authors.affiliation: Department of Pediatrics, JR Sendai Hospital, Sendai, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Morikawa
authors.affiliation: Department of Pediatrics, Sendai National Hospital, Sendai, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Miyabayashi
authors.affiliation: Depatment of Pediatrics, Japanese Red Cross Sendai Hospital, Sendai, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Karahashi Children's Clinic, Sendai, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Karahashi
authors.affiliation: Department of Pediatrics, Funayama Hospital, Yonezawa, Japan.
authors.forename: Seichi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Department of Respiratory and Infectious Diseases, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Tamura
authors.affiliation: Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Department of Health Promotion and Human Behavior, Kyoto University School of Public Health, Kyoto, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Shirakawa
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
mesh_terms: D000293:Adolescent; D000483:Alleles; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003564:Cytidine Deaminase / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000235:genetics; D007564:Japan; D008297:Male; D018895:Microsatellite Repeats; D019001:Nitric Oxide Synthase / Q000235:genetics; D052248:Nitric Oxide Synthase Type I; D011110:Polymorphism, Genetic; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D007371:Interferon-gamma; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase