Table 3

Risk for current wheeze and seroatopy by common GSTP1, GSTM1, GSTT1 polymorphisms and tests for additive interaction

Wheeze, n (%)Overall25/87 (29)39/157 (25)16/53 (30)0.85
No prenatal acetaminophen14/52 (27)18/108 (17)8/35 (23)
Prenatal acetaminophen11/35 (31)21/49 (43)*8/18 (44)0.82 (0.20 to 1.4)¶0.009
Seroatopy§, n (%)Overall18/65 (28)35/111 (32)13/45 (29)0.87
No prenatal acetaminophen11/38 (29)20/74 (27)5/29 (17)
Prenatal acetaminophen7/27 (26)15/37 (41)8/16 (50)*0.75 (0.065 to 1.4)¶0.032
GSTT1 SNPPresentNullRERI (95% CI)
Wheeze, n (%)Overall65/235 (28)16/64 (25)0.67
No prenatal acetaminophen33/156 (21)8/40 (20)
Prenatal acetaminophen32/79 (41)*8/24 (33)−0.37 (−1.8 to 1.0)0.60
Seroatopy, n (%)Overall57/177 (32)10/45 (22)0.19
No prenatal acetaminophen29/114 (25)8/28 (29)
Prenatal acetaminophen28/63 (44)*2/17 (12)0.98 (0.50 to 1.5)<0.001
GSTM1 SNPPresentNullRERI (95% CI)
Wheeze, n (%)Overall64/228 (28)15/61 (25)0.59
No prenatal acetaminophen31/150 (21)8/37 (22)
Prenatal acetaminophen33/78 (42)*7/24 (29)0.38 (–0.63 to 1.4)0.47
Seroatopy, n (%)Overall51/171 (30)14/43 (33)0.73
No prenatal acetaminophen28/110 (26)8/25 (32)
Prenatal acetaminophen23/61 (38)*6/18 (33)0.087 (–0.71 to 0.88)0.83
  • * p<0.05 For the difference in frequency of wheeze/seroatopy between children with and without prenatal acetaminophen exposure.

  • Four common polymorphisms in glutathione S transferases were hypothesised to potentially modify the main effect of prenatal acetaminophen and wheeze. One SNP, GSTT2, was not similarly distributed among the Dominican Republic and African-American children and was therefore not tested in the interaction analysis. The remaining three GST SNPs were tested for interaction with the primary outcome (current wheeze) and one secondary outcome (seroatopy). The GSTP1 allele distribution met Hardy–Weinberg equilibrium criteria (p>0.2 for difference from expected).

  • The statistical significance of effect modification by genotype was assessed by estimating the relative excess risk due to interaction (RERI) and its 95% confidence interval as described by Hosmer and Lemeshow using the fully adjusted model.27 28

  • § Child had specific IgE (>0.35 IU/ml) to at least one allergen tested: dust mite (Dermatophagoides farinae), cockroach, mouse, cat or dog.

  • For the GSTP1 interaction analysis, children with at least one copy of the minor allele (ie, AG or GG) were grouped and compared with those without (eg, AA) based on previous associations with asthma11 13 and altered conjugation kinetics of toxicants related to asthma among individuals with this genotype.15