The GSTP1 gene is a susceptibility gene for childhood asthma and the GSTM1 gene is a modifier of the GSTP1 gene.
BACKGROUND
Bronchial asthma is a chronic airway disorder characterized by bronchial inflammation. Oxidative stress is a key component of inflammation. Glutathione S-transferase P1 (GSTP1), the abundant isoform of glutathione S-transferases (GSTs) in lung epithelium, plays a key role in cellular protection against oxidative stress. Several studies have shown that the GSTP1 geneis involved in the pathogenesis of asthma and a gene-gene interaction may occur within the GST gene superfamily.


METHODS
We screened single-nucleotide polymorphisms (SNPs) at the GSTP1 locus and performed an association study in the Japanese population using two independent case-control groups (group 1: 391 pediatric patients with asthma, 462 adult patients with asthma, and 639 controls, and group 2: 115 pediatric patients with asthma and 184 controls). The effect of GSTM1 null/present genotype on the association between GSTP1 Ile105Val and asthma was also investigated.


RESULTS
We identified 20 SNPs at this locus and found this region consisted of one linkage disequilibrium block represented by four SNPs (tag SNPs). The association between the Ile105Val polymorphism in the GSTP1 gene and childhood asthma was significant in both groups (p = 0.047 in group 1, and p = 0.021 in group 2). This association was only significant in patients with GSTM1-positive genotype in both groups (group 1: GSTM1 present p = 0.013 and GSTM1 null p = 0.925, and group 2: GSTM1 present p = 0.015 and GSTM1 null p = 0.362).


CONCLUSIONS
These findings suggest that the GSTP1 gene is a childhood asthma susceptible gene, and the GSTM1 gene is a modifier gene of GSTP1 for the risk of childhood asthma in the Japanese population.
Kamada
Fumiaki
F
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
Mashimo
Yoichi
Y
Inoue
Hiroki
H
Shao
Chenchen
C
Hirota
Tomomitsu
T
Doi
Satoru
S
Kameda
Makoto
M
Fujiwara
Hiroshi
H
Fujita
Kimie
K
Enomoto
Tadao
T
Sasaki
Sei
S
Endo
Hiroko
H
Takayanagi
Reiko
R
Nakazawa
Chifuyu
C
Morikawa
Toshio
T
Morikawa
Miki
M
Miyabayashi
Shigeaki
S
Chiba
Yasushi
Y
Tamura
Gen
G
Shirakawa
Taro
T
Matsubara
Yoichi
Y
Hata
Akira
A
Tamari
Mayumi
M
Suzuki
Yoichi
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496556:GSTP1 protein, human