Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families.
Childhood-onset asthma is frequently found in association with atopy. Although asthmatic children may develop IgE antibodies against variety of allergens, asthma is associated primarily with allergy to house-dust mites, molds, or other allergens. In this study, we conducted a genome-wide linkage search in 47 Japanese families (197 members) with more than two mite-sensitive atopic asthmatics (65 affected sib-pairs) using 398 markers. Multipoint linkage analysis was carried out for atopic asthma as a qualitative trait using the MAPMAKER/SIB program. We observed significant evidence for linkage with maximum lod scores (MLS) of 4.8 near the interleukin 12 B gene locus on chromosome 5q31-q33. In addition, suggestive evidence on 4q35 with MLS = 2.7 and on 13q11 with MLS = 2.4 was obtained. The other possible linkage regions included 6p22-p21.3 (MLS = 2.1), 12q21-q23 (MLS = 1.9), and 13q14.1-q14.3 (MLS = 2.0). Many of the linkage loci suggested in this study were at or close to those suggested by genome-wide studies for asthma in Caucasian populations. The present study suggests the contribution of the interleukin 12 B gene or nearby gene(s) to mite-sensitive atopic asthma and a considerable number of genetic variants common across Caucasians and Japanese populations contributing to asthma, although the relative importance of various variants may differ between the groups.
Yokouchi
Y
Y
Department of Medical Genetics, University of Tsukuba, Tsukuba, 305-8575, Japan.
Nukaga
Y
Y
Shibasaki
M
M
Noguchi
E
E
Kimura
K
K
Ito
S
S
Nishihara
M
M
Yamakawa-Kobayashi
K
K
Takeda
K
K
Imoto
N
N
Ichikawa
K
K
Matsui
A
A
Hamaguchi
H
H
Arinami
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000208:ethnology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002895:Chromosomes, Human, Pair 5; D005260:Female; D008040:Genetic Linkage; D016678:Genome; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D008925:Mites / Q000276:immunology*
D000485:Allergens; D018664:Interleukin-12