Large scale genotyping study for asthma in the Japanese population.
BACKGROUND
Asthma is a complex phenotype that is influenced by both genetic and environmental factors. Genome-wide linkage and association studies have been performed to identify susceptibility genes for asthma. These studies identified new genes and pathways implicated in this disease, many of which were previously unknown.


OBJECTIVE
To perform a large-scale genotyping study to identify asthma-susceptibility genes in the Japanese population.


METHODS
We performed a large-scale, three-stage association study on 288 atopic asthmatics and 1032 controls, by using multiplex PCR-Invader assay methods at 82,935 single nucleotide polymorphisms (SNPs) (1st stage). SNPs that were strongly associated with asthma were further genotyped in samples from asthmatic families (216 families, 762 members, 2nd stage), 541 independent patients, and 744 controls (3rd stage).


RESULTS
SNPs located in the 5' region of PEX19 (rs2820421) were significantly associated with P < 0.05 through the 1st to the 3rd stage analyses; however, the P values did not reach statistically significant levels (combined, P = 3.8 x 10-5; statistically significant levels with Bonferroni correction, P = 6.57 x 10-7). SNPs on HPCAL1 (rs3771140) and on IL18R1 (rs3213733) were associated with asthma in the 1st and 2nd stage analyses, but the associations were not observed in the 3rd stage analysis.


CONCLUSIONS
No association attained genome-wide significance, but several loci for possible association emerged. Future studies are required to validate these results for the prevention and treatment of asthma.
Imada
Yoshiko
Y
Department of Medical Genetics, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, 305-8577 Japan. mija-12@comet.ocn.ne.jp
Fujimoto
Masaya
M
Hirata
Kenji
K
Hirota
Tomomitsu
T
Suzuki
Yoichi
Y
Saito
Hirohisa
H
Matsumoto
Kenji
K
Akazawa
Akira
A
Katsunuma
Toshio
T
Yoshihara
Shigemi
S
Ebisawa
Motohiro
M
Shibasaki
Masanao
M
Arinami
Tadao
T
Tamari
Mayumi
M
Noguchi
Emiko
E