Overview of the published variants, the implicated pathways and the described effect
| Pathway | Protein family | Associated gene | Variant (associated SNP if reported) | Functional impact | Effect in interaction with AAP | Reference |
| Antioxidant defences | Glutathione-S-transferase | GSTM1 | Null genotype | No functional protein | Significant reductions in FEF25-75% after ozone exposure (2.9% decrease, CI 0.6–5.2, per 50 ppb increase in ozone). | Romieu et al. [58] |
| GSTP1 | GSTP1 I/I at codon 105 (rs947894) | Change in catalytic properties | Higher childhood asthma incidence for those living in a high air pollution district (adjusted OR 5.52, CI 1.64–21.25). | Lee et al. [59] | ||
| Higher risk for childhood asthma for those living in a community with low PM10 concentrations (no effect size reported). | Su et al. [60] | |||||
| Negative association between PM2.5 and ozone and childhood asthma (adjusted OR 0.6, CI 0.45–0.82 and 0.74, CI 0.6–0.9, respectively). | Hwang et al. [61] | |||||
| GSTP1 I/V or V/V at codon 105 (rs947894) | Change in catalytic properties | Increased risk of allergic sensitisation with increasing NOx exposure (OR 2.4, CI 1.0–5.3 for difference between fifth and 95th percentile exposure). | Melén et al. [55] | |||
| Higher risk for childhood asthma for those living in a community with high PM10 concentrations (no effect size reported). | Su et al. [60] | |||||
| Positive association between PM2.5 and ozone and childhood asthma (adjusted OR 1.52, CI 1.01–2.27 and 1.19, CI 0.91–1.57, respectively). | Hwang et al. [61] | |||||
| NAD(P)H dehydrogenase 1 | NQO1 | At least one S at codon 187# | Lower enzymatic activity | Significantly reduced asthma risk as opposed to P/P homozygotic subjects (risk ratio 0.4, CI 0.2–0.8). | David et al. [63] | |
| Microsomal EPH | EPHX1 | Y at codon 113 and R at codon 139¶ | Higher enzymatic activity | Increased risk for asthma in children with high enzymatic activity living near a major road (risk ratio 3.2, CI 1.75–6.00). | Salam et al. [65] | |
| Catalase | CAT | G/G at codon 330 (rs1001179)+ | Decreased enzymatic activity | Increased respiratory-related school absences in communities with high NO2 (risk ratio 1.53 with CI 1.09–2.14). | Wenten et al. [66] | |
| Myeloperoxidase | MPO | G/A or A/A at codon 463 (rs2333227)+ | Decreased enzymatic activity | Increased respiratory related school absences in communities with high NO2 (risk ratio 1.53 with CI 1.09–2.14). | Wenten et al. [66] | |
| Heme oxygenase-1 | HMOX-1 | Fewer than 23 (GT)n repeats | Decreased inducibility | Reduced risk for now-onset asthma in non-Hispanic white children (HR 0.64, CI 0.41–0.99). | Islam et al. [68] | |
| Thioredoxin reductase | TXNDC8 | rs7041938 T>G | Not described | Significant interaction with NO2 exposure in Caucasian children with asthma (no effect size reported). | Ierodiakonou et al. [70] | |
| Intrinsic oxidative load | Cytochrome P450 2E1 protein | CYP2E1 | rs2070673 AT or TT genotype | Not described | Increased odds for asthma in children living in an area with high B[a]P exposure (OR 5, CI 3.1–8.8). | Choi et al. [35] |
| B4GALT5 | B4GALT5 | rs686237 A>C | Increased expression | Significant interaction with NO2 at birth address and childhood asthma (no effect size reported). | Gref et al. [72] | |
| Nitrosative stress | Arginase | ARG1 | rs2749935 A>T | Not described | Reduced asthma risk amongst atopic children in high ozone communities (OR per haplotype copy 0.12, CI 0.04–0.43). | Salam et al. [76] |
| Immune response | Tumour necrosis factor | TNF-α | G/G at position 308 of the TNF-α gene promoter§ | Decreased expression | Decreased wheezing incidence in children living in low ozone communities (OR 0.5, CI 0.4–0.7). | Li et al. [82] |
| Toll-like receptor | TLR-2 | rs4696480 T>A | Not described | Increased risk for asthma with increasing PM2.5 exposure (OR 2.0, CI 1.2–3.1 for every interquartile range increase). | Kerkhof et al. [83] | |
| TLR-4 | rs2770150 TC rs10759931 GG rs6478317 GG rs10759932 CT or CC rs1927911 TT | Not described | Increased risk for asthma with increasing PM2.5 exposure (OR 2.0, CI 1.1–3.6; OR 2.6, CI 1.4–4.9; OR 2.2, CI 1.2–4.3; OR 2.9, CI 1.2–6.9; OR 4.4, CI 1.7–11.7). | Kerkhof et al. [83] | ||
| Cytotoxic T-lymphocyte-associated protein 4 | CTLA4 | rs11571316 G>A rs11571319 G>A | Suspected decreased enzymatic activity | Increased odds for asthma in children living in an area with high B[a]P exposure (OR 9, CI 4.56–18.36 and OR 8, CI 3.95–14.2, respectively). | Choi et al. [35] | |
| Signal transducer and activator of transcription 4 | STAT4 | rs1031509 TG or GG | Not described | Increased odds for asthma in children living in an area with high B[a]P exposure (OR 5, CI 3.03–8.55). | Choi et al. [35] | |
| Eph receptor | EPHA3 | rs13090972 T>G rs958144 C>T | Not described | Significant interaction with NO2 exposure in Caucasian children with asthma. | Ierodiakonou et al. [70] | |
| Repair and remodelling | Transforming growth factor B1 | TGF-B1 | T/T at codon 509 (rs4803457) | Not described | Higher risk for early persistent asthma in children with this genotype living near a highway (risk ratio 3, CI 1.29–7.44). | Salam et al. [88] |
| Adenylyl cyclase type 2 | ADCY2 | rs6886921 C>T | Not described | Significant interaction with NO2 at birth address and childhood asthma. | Gref et al. [72] |
AAP: ambient air pollution; B4GALT4: beta-1,4-galactosyltransferase 1; CI: confidence interval; EPHX1: epoxide hydrolase 1; FEF25–75%: forced mid-expiratory flow at 25–75% of forced vital capacity; GSTM1: glutathione S-transferase Mu 1; GSTP1: glutathione-S-transferase Pi 1; HR: hazard ratio; NAD(P)H: nicotinamide adenine dinucleotide phosphate; OR: odds ratio; PM: particulate matter; SNP: single nucleotide polymorphism. #: reported effect in patients with GSTM1 null genotypes; ¶: reported effect in patients with GSTP1 V/V genotypes; +: reported effect in patients with variants in both genes; §: effect decreased in patients with GTSM1 null or GSTP V at codon 105 genotype.