Linkage and association of childhood asthma with the chromosome 12 genes.
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).
Shao
Chenchen
C
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.
Suzuki
Yoichi
Y
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.
Kamada
Fumiaki
F
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kanno
Kiyoshi
K
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Tamari
Mayumi
M
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Hasegawa
Koichi
K
Laboratory for Genetics of Allergic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
Aoki
Yoko
Y
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kure
Shigeo
S
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Yang
Xue
X
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Endo
Hiroko
H
Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Japan.
Takayanagi
Reiko
R
Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Japan.
Nakazawa
Chifuyu
C
Department of Pediatrics, Tohoku Rosai Hospital, Sendai, Japan.
Morikawa
Toshio
T
Morikawa Children's Clinic, Sendai, Japan.
Morikawa
Miki
M
Department of Pediatrics, JR Sendai Hospital, Sendai, Japan.
Miyabayashi
Shigeaki
S
Department of Pediatrics, Sendai National Hospital, Sendai, Japan.
Chiba
Yasushi
Y
Depatment of Pediatrics, Japanese Red Cross Sendai Hospital, Sendai, Japan.
Karahashi
Minoru
M
Karahashi Children's Clinic, Sendai, Japan.
Saito
Seichi
S
Department of Pediatrics, Funayama Hospital, Yonezawa, Japan.
Tamura
Gen
G
Department of Respiratory and Infectious Diseases, Tohoku University School of Medicine, Sendai, Japan.
Shirakawa
Taro
T
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.
Matsubara
Yoichi
Y
Department of Medical Genetics, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
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)
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