Interactions between traffic air pollution and glutathione S-transferase genes on childhood asthma

Table 1 Primer and probe sequences for GSTP1, GSTM1 and GSTT1 genes variants

Gene	Sequence
GSTP1 (Ile105Val)
Forward primer	5’-CCTGGTGGACATGGTGAATG-3’
Reverse primer	5’-TGCTCACATAGTTGGTGTAGATGA-3’
Prob for Ile allele	5’-(VIC)CTGCAAATACGTCTCC-3’
Prob for Val allele	5’-(6FAM)TGCAAATACATCTCCCT-3’
GSTM1
Forward primer	5’-GGAAACAAGGTAAAGGAGGAGTGAT-3’
Reverse primer	5’-CAAGAATATGTGGGCTGGAACCT-3’
Prob	5’-ACGTGAAGCAAAACAG-3’
GSTT1
Forward primer	5’-GTGGTCCCCAAATCAGATGCT-3’
Reverse primer	5’-GCACCCACGGGCTGT-3’
Prob	5’-CCCTGCCCTCACAACC-3’

Table 2 Selected characteristics for participants in Taiwan children health study n (%)

	With genotyping	All eligible participants
	(n = 3714)	(n = 5045)
Demographic information
Sex
Boys	1820 (49.0)	2436 (48.3)
Girls	1894 (51.0)	2609 (51.7)
Age, yr (mean ± SD)	12.8 ± 0.4	12.9 ± 0.6
Parental education, yr1
≤ 12	2301 (62.0)	3176 (63.5)
13-15	734 (19.8)	956 (19.1)
≥ 16	674 (18.2)	873 (17.4)
Gestational age1
Full term	3318 (90.9)	4461 (90.7)
< 4 wk early	236 (6.5)	316 (6.4)
≥ 4 wk early	98 (2.7)	142 (2.9)
Parental history of atopy1
Yes	952 (26.5)	1257 (25.9)
No	2645 (73.5)	3590 (74.1)
Family income12
≤ 400000	1233 (35.7)	1751 (37.5)
410000-800000	1402 (40.6)	1844 (39.5)
≥ 810000	822 (23.8)	1072 (23.0)
Number of siblings1
0	346 (9.3)	458 (9.1)
1	1748 (46.9)	2265 (45.0)
2	1229 (33.0)	1697 (33.7)
≥ 3	406 (10.9)	613 (12.2)
Home exposures1
Dampness at home	1915 (51.6)	2610 (51.7)
In utero exposure maternal smoking	141 (3.8)	193 (3.8)
ETS at home	1597 (43.2)	2246 (44.8)
Respiratory outcomes1
Asthma	289 (7.8)	372 (7.4)
Asthma under medication	95 (2.6)	122 (2.4)
Wheeze	443 (12.0)	583 (11.6)
Early-onset asthma	186 (5.2)	239 (4.9)
Late-onset asthma	95 (2.7)	121 (2.5)
Active asthma	136 (3.7)	168 (3.4)
Genetic markers1
GSTP1
Ile/Ile	2433 (65.5)
Ile/Val	1132 (30.5)
Val/Val	149 (4.0)
GSTM1
Present	1596 (43.0)
Null	2118 (57.0)
GSTT1
Present	1923 (51.8)
Null	1791 (48.2)

¹Number of subjects do not add up to total N because of missing data;

²New Taiwan dollars per year ($1 US = $ 33 New Taiwan). ETS: Environmental tobacco smoke.

Table 3 Association of ambient NO₂ and glutathione S-transferases genotypes with asthma phenotypes

	Asthma		Early-onset asthma		Late-onset asthma		Active asthma		Asthma under medication		Wheeze
	OR	95%CI	OR	95%CI	OR	95%CI	OR	95%CI	OR	95%CI	OR	95%CI
NO2	1.03	(0.80, 1.32)	1.03	(0.76, 1.39)	1.1	(0.72, 1.66)	1.16	(0.82, 1.65)	1.33	(0.87, 2.03)	1.08	(0.88, 1.32)
GSTP1
Co-dominant model
Ile/Ile	1		1		1		1		1		1
Ile/Val	0.98	(0.75, 1.28)	0.99	(0.71, 1.38)	1.01	(0.64, 1.61)	1.01	(0.69, 1.49)	0.94	(0.59, 1.49)	1.03	(0.82, 1.28)
Val/Val	0.80	(0.41, 1.57)	0.50	(0.18, 1.39)	1.47	(0.62, 3.51)	1.07	(0.45, 2.54)	1.30	(0.50, 3.34)	0.99	(0.59, 1.66)
Dominant model
Ile/Ile	1		1		1		1		1		1
Ile/Val or Val/Val	0.96	(0.74, 1.24)	0.93	(0.68, 1.29)	1.07	(0.69, 1.66)	1.02	(0.70, 1.48)	0.98	(0.63, 1.52)	1.02	(0.82, 1.27)
Additive model
Val allele	0.95	(0.76, 1.18)	0.89	(0.67, 1.17)	1.11	(0.78, 1.58)	1.02	(0.75, 1.39)	1.02	(0.71, 1.48)	1.01	(0.85, 1.21)
GSTM1
Null	0.89	(0.69, 1.13)	0.83	(0.62, 1.13)	0.94	(0.62, 1.43)	0.88	(0.62, 1.26)	0.81	(0.54, 1.23)	0.99	(0.81, 1.22)
GSTT1
Null	1.18	(0.92, 1.51)	1.29	(0.95, 1.75)	1.04	(0.69, 1.58)	1.43	(1.00, 2.03)	1.47	(0.96, 2.23)	1.16	(0.95, 1.42)

Models are adjusted for age, sex, family income, parental education, parental history of atopy, number of siblings, in utero exposures to maternal smoking, environmental tobacco smoke at home, gestational age and dampness at home.

Table 4 Association of ambient NO₂ level with asthma phenotypes, stratified by GSTP1 genotypes

	GSTT1				P for interaction
	Ile/Ile		Ile/Val or Val/Val
	OR	95%CI	OR	95%CI
Asthma
Low NO2	1		1		0.003
High NO2	0.78	(0.57, 1.06)	1.76	(1.15, 2.70)
Early-onset asthma
Low NO2	1		1		0.10
High NO2	0.88	(0.60, 1.29)	1.45	(0.86, 2.47)
Late-onset asthma
Low NO2	1		1		0.01
High NO2	0.63	(0.37, 1.07)	2.59	(1.24, 5.41)
Active asthma
Low NO2	1		1		0.06
High NO2	0.89	(0.57, 1.39)	1.93	(1.05, 3.57)
Asthma under medication
Low NO2	1		1		0.02
High NO2	0.88	(0.52, 1.49)	2.95	(1.37, 6.32)
Wheeze
Low NO2	1		1		0.01
High NO2	0.90	(0.69, 1.16)	1.54	(1.09, 2.18)

Models are adjusted for age, sex, family income, parental education, parental history of atopy, number of siblings, in utero exposures to maternal smoking, environmental tobacco smoke at home, gestational age and dampness at home.

Table 5 Association of ambient NO₂ level with asthma phenotypes, stratified by GSTM1 genotypes

	GSTT1				P for interaction
	Present		Null
	OR	95%CI	OR	95%CI
Asthma
Low NO2	1		1		0.87
High NO2	1.11	(0.76, 1.60)	0.98	(0.70, 1.38)
Early-onset asthma
Low NO2	1		1		0.79
High NO2	1.02	(0.65, 1.59)	1.01	(0.66, 1.54)
Late-onset asthma
Low NO2	1		1		0.68
High NO2	1.33	(0.71, 2.50)	1.02	(0.58, 1.78)
Active asthma
Low NO2	1		1		0.97
High NO2	1.18	(0.69, 2.01)	1.16	(0.72, 1.87)
Asthma under medication
Low NO2	1		1		0.61
High NO2	1.16	(0.62, 2.16)	1.50	(0.84, 2.69)
Wheeze
Low NO2	1		1		0.75
High NO2	1.05	(0.76, 1.44)	1.10	(0.84, 1.44)

Models are adjusted for age, sex, family income, parental education, parental history of atopy, number of siblings, in utero exposures to maternal smoking, environmental tobacco smoke at home, gestational age and dampness at home.

Table 6 Association of ambient NO₂ level with asthma phenotypes, stratified by GSTT1 genotypes

	GSTT1				P for interaction
	Present		Null
	OR	95%CI	OR	95%CI
Asthma
Low NO2	1		1		0.96
High NO2	1.09	(0.76, 1.57)	0.99	(0.70, 1.39)
Early-onset asthma
Low NO2	1		1		0.39
High NO2	1.29	(0.82, 2.05)	0.87	(0.58, 1.32)
Late-onset asthma
Low NO2	1		1		0.39
High NO2	0.96	(0.52, 1.75)	1.24	(0.69, 2.24)
Active asthma
Low NO2	1		1		0.66
High NO2	1.31	(0.76, 2.28)	1.07	(0.67, 1.71)
Asthma under medication
Low NO2	1		1		0.23
High NO2	1.96	(1.00, 3.84)	1.03	(0.59, 1.79)
Wheeze
Low NO2	1		1		0.33
High NO2	1.23	(0.91, 1.66)	0.96	(0.73, 1.28)

Models are adjusted for age, sex, family income, parental education, parental history of atopy, number of siblings, in utero exposures to maternal smoking, environmental tobacco smoke at home, gestational age and dampness at home.