Study Inclusion and Characteristics
The flow chart of the selection process is shown in Fig. 1. Briefly, a total of 1913 articles were identified after initial search, of which, 868 duplicate articles were removed. After screening the titles and abstracts, 270 articles were selected. The 270 full-text articles were evaluated based on inclusive and exclusive criteria. Finally, 45 articles were included in the meta-analysis, including 7592 asthma patients and 7671 controls. The included studies were published between 2010 and 2020 and were conducted in ten countries: China, Indian, Egypt, Jordan, Poland, Mexico, Saudi Arabia, Colombia, Turkey and Tunisia. A total of 18 polymorphisms in 7 genes were identified for data synthesis: IL-13 + 2044G/A (rs20541)10–14, IL-13 -1112C/T(rs1800925)11,13,15−18, IL-13 + 1923C/T (rs1295686)19,20, IL-4 -590C/T (rs2243250)12,15–18,20−25, ADRB2 -46 G /A(rs1042713)11,20,26−31, ADRB2 -79G/C (rs1042713)26,28−32, ADAM33 F + 1(rs511898)33–36, ADAM33 V4 (rs2787094)33,34,37−39, ADAM33 S2(rs528557)33,35,38,39, ADAM33 T2 (rs2280090)34,37−39, ADAM33 T1(rs2280091)34,35,38,39, ADAM33 ST + 4 (rs44707)33,40,41, ORMDL3 rs721638942–44, VDR ApaⅠ (rs7975232)45–49, VDR FokⅠ (rs2228570)45–47,49−51,VDR BsmⅠ (rs1544410)46–49, 51, VDR TaqⅠ (rs731236)45–47, 49, and CTLA-4 + 49 G/A (rs231775)52–54. The detailed characteristics of included studies are given in Table 1.
Results of meta-analysis
The results of meta-analyses of the association between each polymorphism and the risk of pediatric asthma in the total population and in Asian are shown in Table 2.
Table 2
Meta-analysis of the association between SNPs of 18 genes and pediatric asthma risk
Gene SNPs | Comparison | N | Test of association | | Test of heterogeneity | | | Begg’s test |
OR | 95%CI | P | | Model | P | I2/% | | z | p |
IL-13 + 2044G/A rs20541 | A vs G | 5 | 1.52 | 1.15–2.01 | 0.004 | | R | 0.01 | 69 | | 2.20 | 0.03 |
AA vs GG | 1.73 | 0.90–3.35 | 0.10 | | R | 0.02 | 66 | | 0.73 | 0.46 |
GA vs GG | 1.79 | 1.18–2.72 | 0.006 | | R | 0.01 | 69 | | 1.71 | 0.09 |
GA + AA vs GG | 1.80 | 1.14–2.28 | 0.01 | | R | 0.002 | 76 | | 1.71 | 0.09 |
AA vs GA + GG | 0.99 | 0.78–1.25 | 0.94 | | F | 0.13 | 44 | | 1.22 | 0.22 |
Asians | A vs G | 3 | 1.93 | 1.51–2.48 | <0.00001 | | F | 0.49 | 0 | | - | - |
GA + AA vs GG | 2.56 | 1.83–3.58 | <0.00001 | | F | 0.30 | 17 | | - | - |
IL-13 -1112C/T rs1800925 | T vs C | 6 | 0.63 | 0.16–2.56 | 0.52 | | R | <0.00001 | 99 | | 0.75 | 0.45 |
TT vs CC | | 1.27 | 0.61–2.63 | 0.53 | | R | <0.00001 | 86 | | 0.75 | 0.45 |
CT vs CC | | 1.19 | 0.72–1.97 | 0.49 | | R | <0.00001 | 90 | | 0.00 | 1.00 |
CT + TT vs CC | | 1.18 | 0.71–1.96 | 0.59 | | R | <0.00001 | 92 | | 1.13 | 0.26 |
TT vs CT + CC | | 1.11 | 0.59–2.09 | 0.75 | | R | <0.0001 | 83 | | 0.75 | 0.45 |
Asians | T vs C | 5 | 1.16 | 0.68–1.96 | 0.59 | | R | <0.00001 | 93 | | - | - |
CT + TT vs CC | | 1.28 | 0.67–2.43 | 0.45 | | R | <0.00001 | 93 | | - | - |
IL-13 + 1923C/T rs1295686 | T vs C | 3 | 1.34 | 0.79–2.27 | 0.28 | | R | 0.0009 | 86 | | 1.04 | 0.30 |
TT vs CC | | 1.61 | 0.59–4.40 | 0.35 | | R | 0.01 | 77 | | 1.04 | 0.30 |
CT vs CC | | 1.38 | 0.67–2.87 | 0.38 | | R | 0.002 | 84 | | 1.04 | 0.30 |
CT + TT vs CC | | 1.44 | 0.71–2.95 | 0.32 | | R | 0.001 | 85 | | 1.04 | 0.30 |
TT vs CT + CC | | 1.42 | 0.54–3.69 | 0.48 | | R | 0.01 | 78 | | 0.00 | 1.00 |
IL-4 -590C/T rs2243250 | T vs C | 12 | 1.22 | 0.97–1.54 | 0.09 | | R | <0.00001 | 81 | | 0.48 | 0.63 |
TT vs CC | | 1.55 | 1.08–2.22 | 0.02 | | R | 0.01 | 53 | | 0.75 | 0.45 |
CT vs CC | | 1.29 | 1.06–1.56 | 0.01 | | F | 0.06 | 42 | | 0.21 | 0.84 |
CT + TT vs CC | | 1.44 | 1.06–1.95 | 0.02 | | R | 0.01 | 55 | | 0.21 | 0.84 |
TT vs CT + CC | | 1.28 | 1.05–1.55 | 0.01 | | R | 0.02 | 53 | | 1.58 | 0.12 |
Asians | T vs C | 10 | 1.20 | 0.91–1.57 | 0.19 | | R | <0.00001 | 84 | | - | - |
| CT + TT vs CC | | 1.45 | 0.96–2.19 | 0.08 | | R | 0.005 | 62 | | - | - |
Chinese | T vs C | | 1.25 | 0.92–1.69 | 0.15 | | R | <0.00001 | 84 | | - | - |
| CT + TT vs CC | 9 | 1.79 | 1.38–2.33 | <0.0001 | | F | 0.38 | 7 | | - | - |
ADRB2 -46 G /A rs1042713 | G vs A | 8 | 1.00 | 0.52–1.02 | 0.99 | | R | <0.00001 | 85 | | 0.37 | 0.71 |
GG vs AA | | 1.04 | 0.63–1.01 | 0.87 | | R | <0.00001 | 82 | | 0.37 | .071 |
GA vs AA | | 1.09 | 0.84–1.42 | 0.51 | | R | 0.04 | 52 | | 1.86 | 0.06 |
GA + GG vs AA | | 1.08 | 0.78–1.48 | 0.64 | | R | 0.0009 | 72 | | 0.62 | 0.54 |
GG vs GA + AA | | 0.96 | 0.63–1.46 | 0.83 | | R | <0.00001 | 83 | | 0.87 | 0.39 |
Asians | G vs A | 4 | 0.88 | 0.55–1.41 | 0.60 | | R | <0.00001 | 91 | | - | - |
GA + GG vs AA | | 1.03 | 0.63–1.67 | 0.91 | | R | 0.0003 | 81 | | - | - |
ADRB2 -79G/C rs1042713 | G vs C | 6 | 1.14 | 0.88–1.48 | 0.31 | | R | 0.04 | 56 | | 0.75 | 0.45 |
GG vs CC | | 1.19 | 0.06–1.56 | 0.46 | | F | 0.63 | 0 | | 0.75 | 0.45 |
GC vs CC | | 1.14 | 0.62–1.42 | 0.22 | | F | 0.08 | 48 | | 0.00 | 1.00 |
GC + GG vs CC | | 1.18 | 0.87–1.61 | 0.28 | | R | 0.05 | 54 | | 0.75 | 0.45 |
GG vs GC + CC | | 1.09 | 0.69–1.70 | 0.72 | | F | 0.71 | 0 | | 0.38 | 0.71 |
Asians | G vs C | 3 | 1.08 | 0.65–1.80 | 0.75 | | R | 0.005 | 81 | | - | - |
GC + GG vs CC | | 1.12 | 0.63–1.98 | 0.71 | | R | 0.008 | 79 | | - | - |
ADAM33 F + 1 rs511898 | T vs C | 5 | 1.33 | 0.99–1.79 | 0.06 | | R | 0.0004 | 80 | | -0.24 | 1.00 |
TT vs CC | | 1.81 | 0.95–3.44 | 0.07 | | R | 0.0007 | 79 | | -0.24 | 1.00 |
CT vs CC | | 1.13 | 0.93–1.36 | 0.21 | | F | 0.93 | 0 | | 0.73 | 0.46 |
CT + TT vs CC | | 1.24 | 1.04–1.48 | 0.02 | | F | 0.13 | 44 | | 0.24 | 0.81 |
TT vs TC + CC | | 1.67 | 0.94–2.97 | 0.08 | | R | 0.0007 | 79 | | 0.24 | 0.81 |
Asians | T vs C | 4 | 1.23 | 0.90–1.67 | 0.19 | | R | 0.008 | 75 | | - | - |
CT + TT vs CC | | 1.15 | 0.94–1.40 | 0.18 | | F | 0.26 | 25 | | - | - |
ADAM33 V4 rs2787094 | G vs C | 5 | 0.99 | 0.47–2.09 | 0.99 | | R | <0.00001 | 97 | | -0.24 | 1.00 |
GG vs CC | | 1.22 | 0.34–4.32 | 0.76 | | R | <0.00001 | 94 | | 0.24 | 0.81 |
GC vs CC | | 1.17 | 0.66–2.08 | 0.59 | | R | 0.0006 | 79 | | 0.73 | 0.46 |
GC + GG vs CC | | 1.02 | 0.47–2.22 | 0.96 | | R | <0.00001 | 90 | | 1.22 | 0.22 |
CC vs CG + CC | | 1.15 | 0.44–3.01 | 0.78 | | R | <0.00001 | 95 | | 0.24 | 0.81 |
ADAM33 S2 rs528557 | G vs C | 4 | 0.78 | 0.28–2.11 | 0.65 | | R | <0.00001 | 97 | | 0.34 | 0.73 |
GG vs CC | | 0.66 | 0.10–4.60 | 0.68 | | R | <0.00001 | 96 | | 1.02 | 0.31 |
GC vs CC | | 0.84 | 0.38–1.83 | 0.66 | | R | <0.00001 | 89 | | 1.70 | 0.90 |
GC + GG vs CC | | 0.73 | 0.25–2.18 | 0.58 | | R | <0.00001 | 95 | | 1.02 | 0.31 |
GG vs GC + CC | | 0.76 | 0.17–3.47 | 0.73 | | R | <0.00001 | 95 | | 0.34 | 0.73 |
Asians | G vs C | 3 | 0.73 | 0.18-3.00 | 0.66 | | R | <0.00001 | 98 | | - | - |
GC + GG vs CC | | 0.67 | 0.15–3.04 | 0.60 | | R | <0.00001 | 97 | | - | - |
ADAM33 T2 rs2280090 | A vs G | 4 | 1.86 | 1.10–3.15 | 0.02 | | R | <0.0001 | 86 | | -0.34 | 1.00 |
AA vs GG | | 4.25 | 2.27–7.98 | <0.00001 | | F | 0.15 | 43 | | 0.34 | 0.73 |
AG vs GG | | 1.71 | 1.03–2.85 | 0.04 | | R | 0.002 | 79 | | -0.34 | 1.00 |
AG + AA vs GG | | 1.87 | 1.07–3.27 | 0.03 | | R | 0.0003 | 84 | | -0.34 | 1.00 |
AA vs GA + GG | | 3.72 | 1.98–6.98 | <0.0001 | | F | 0.27 | 23 | | 0.34 | 0.73 |
Asians | A vs G | 3 | 2.26 | 1.29–3.94 | 0.004 | | R | 0.002 | 85 | | - | - |
AG + AA vs GG | | 2.29 | 1.25–4.17 | 0.007 | | R | 0.002 | 83 | | - | - |
ADAM33 T1 rs2280091 | G vs A | 4 | 1.54 | 0.90–2.65 | 0.12 | | R | <0.00001 | 90 | | 1.70 | 0.90 |
GG vs AA | | 4.11 | 2.56–5.90 | <0.00001 | | F | 0.03 | 67 | | 1.02 | 0.31 |
GA vs AA | | 2.05 | 1.37–3.08 | 0.0005 | | R | 0.06 | 60 | | 0.34 | 0.73 |
GA + GG vs AA | | 2.12 | 1.29–3.47 | 0.003 | | R | 0.007 | 75 | | 1.02 | 0.31 |
TT vs TC + CC | | 1.70 | 0.65–4.45 | 0.28 | | R | <0.0001 | 87 | | 0.34 | 0.73 |
Asians | G vs A | 3 | 1.72 | 0.95–3.14 | 0.08 | | R | <0.0001 | 91 | | - | - |
GA + GG vs AA | | 2.92 | 2.35–3.63 | <0.00001 | | F | 0.34 | 8 | | - | - |
ADAM33 ST + 4 rs44707 | C vs A | 3 | 1.57 | 1.32–1.87 | <0.00001 | | F | 0.62 | 0 | | 0.00 | 1.00 |
CC vs AA | | 2.19 | 1.55–3.12 | <0.0001 | | F | 0.56 | 0 | | 1.04 | 0.30 |
AC vs AA | | 1.59 | 1.18–2.13 | 0.002 | | F | 0.16 | 45 | | 1.04 | 0.30 |
AC + CC vs AA | | 1.81 | 1.37–2.39 | <0.0001 | | F | 0.37 | 0 | | 1.04 | 0.30 |
CC vs AC + AA | | 1.74 | 1.31–2.30 | 0.0001 | | F | 0.47 | 0 | | 0.00 | 1.00 |
ORMDL3 rs7216389 | T vs C | 3 | 1.81 | 1.45–2.25 | <0.00001 | | F | 0.76 | 0 | | 0.00 | 1.00 |
TT vs CC | | 3.35 | 1.24–7.57 | <0.00001 | | F | 0.09 | 0 | | 0.00 | 1.00 |
CT vs CC | | 1.98 | 1.11–3.56 | 0.02 | | F | 0.94 | 0 | | 0.00 | 1.00 |
CT + TT vs CC | | 2.76 | 1.58–4.82 | 0.0004 | | F | 0.92 | 0 | | 0.00 | 1.00 |
TT vs TC + CC | | 1.89 | 1.44–2.47 | <0.00001 | | F | 0.84 | 0 | | 0.00 | 1.00 |
VDR ApaⅠ rs7975232 | C vs A | 5 | 1.31 | 1.06–1.62 | 0.01 | | F | 0.12 | 46 | | 1.22 | 0.22 |
CC vs AA | | 1.94 | 1.17–3.24 | 0.01 | | F | 0.23 | 31 | | -0.34 | 1.00 |
AC vs AA | | 2.18 | 1.34–3.56 | 0.002 | | F | 0.78 | 0 | | -0.34 | 1.00 |
AC + CC vs AA | | 1.95 | 1.26–3.01 | 0.003 | | F | 0.38 | 2 | | 0.34 | 0.73 |
CC vs AC + AA | | 1.36 | 0.84–2.21 | 0.21 | | R | 0.06 | 55 | | 0.73 | 0.46 |
Asians | C vs A | 3 | 1.60 | 1.13–2.27 | 0.008 | | F | 0.32 | 12 | | - | - |
AC + CC vs AA | | 2.10 | 0.64–6.90 | 0.22 | | R | 0.10 | 63 | | - | - |
VDR FokⅠ rs2228570 | T vs C | 6 | 1.36 | 0.99–1.86 | 0.06 | | R | 0.03 | 60 | | 0.38 | 0.71 |
TT vs CC | | 1.85 | 0.93–3.70 | 0.08 | | R | 0.04 | 57 | | 0.75 | 0.45 |
TC vs CC | | 1.27 | 0.91–1.76 | 0.16 | | F | 0.21 | 30 | | 0.38 | 0.71 |
TC + TT vs CC | | 1.39 | 1.02–1.89 | 0.04 | | F | 0.07 | 50 | | 0.75 | 0.45 |
TT vs TC + CC | | 1.50 | 1.12–2.01 | 0.006 | | F | 0.17 | 36 | | 0.00 | 1.00 |
Asians | T vs C | 3 | 1.13 | 0.68–1.89 | 0.64 | | R | 0.05 | 67 | | - | - |
TC + TT vs CC | | 1.10 | 0.72–1.70 | 0.65 | | F | 0.31 | 13 | | - | - |
VDR BsmⅠ rs1544410 | A vs G | 5 | 1.47 | 1.15–1.88 | 0.002 | | F | 0.24 | 27 | | 1.71 | 0.09 |
AA vs GG | | 1.79 | 1.03–3.11 | 0.04 | | F | 0.22 | 34 | | 0.00 | 1.00 |
AG vs GG | | 1.91 | 1.02–3.58 | 0.04 | | R | 0.08 | 51 | | 0.24 | 0.81 |
AG + AA vs GG | | 1.61 | 1.16–2.25 | 0.005 | | F | 0.15 | 41 | | 1.22 | 0.22 |
AA vs AG + GG | | 1.74 | 1.05–2.88 | 0.03 | | F | 0.19 | 42 | | 0.00 | 1.00 |
Asians | A vs G | 4 | 1.81 | 1.15–2.85 | 0.01 | | F | 0.20 | 36 | | - | - |
AG + AA vs GG | | 2.26 | 1.34–3.82 | 0.002 | | F | 0.22 | 32 | | - | - |
VDR TaqⅠ rs731236 | C vs T | 4 | 0.81 | 0.50–1.30 | 0.38 | | R | 0.01 | 72 | | 1.02 | 0.31 |
CC vs TT | | 0.90 | 0.27–2.97 | 0.18 | | R | 0.008 | 79 | | 0.00 | 1.00 |
CT vs TT | | 1.09 | 0.40–2.97 | 0.86 | | R | 0.001 | 81 | | 1.02 | 0.31 |
CT + CC vs TT | | 0.93 | 0.37–2.29 | 0.87 | | R | 0.002 | 80 | | 1.02 | 0.31 |
CC vs CT + TT | | 0.63 | 0.26–1.54 | 0.31 | | R | 0.01 | 77 | | 0.00 | 1.00 |
CTLA-4 + 49 A/G rs231775 | A vs G | 3 | 1.22 | 0.52–2.88 | 0.64 | | R | 0.002 | 84 | | 0.00 | 1.00 |
AA vs GG | | 1.48 | 0.30–7.40 | 0.63 | | R | 0.007 | 80 | | 0.00 | 1.00 |
AG vs GG | | 1.28 | 0.84–1.95 | 0.24 | | F | 0.20 | 37 | | 1.04 | 0.30 |
AG + AA vs GG | | 1.20 | 0.50–2.89 | 0.68 | | R | 0.03 | 71 | | 0.00 | 1.00 |
AA vs AG + GG | | 1.51 | 0.40–5.70 | 0.54 | | R | 0.02 | 74 | | 0.00 | 1.00 |
SNPs: single nucleotide polymorphisms, N: number of studies, OR: odds ratio, 95% CI: 95% confidence interval, R: random-effect model, F: fixed-effect model |
IL-13 + 2044G/A polymorphism and pediatric asthma risk
The association between IL-13 + 2044G/A polymorphism and pediatric asthma risk was evaluated in 5 case-control studies, including 921 cases and 920 controls. The result of meta-analysis shown that the AG and AG + AA genotypes was associated with pediatric asthma risk when compared with GG genotype (AG vs GG: OR = 1.79, 95% CI:1.18–2.72, P = 0.006; GA + AA vs GG: OR = 1.80, 95% CI:1.14–2.28, P = 0.01) in random-effects model. And allele A was associated with increased risk of pediatric asthma (A vs G: OR = 1.52, 95% CI:1.15–2.01, P = 0.004). No association between gene polymorphism and asthma risk was found in homozygous and recessive models. Subgroup analysis showed that a significant increased risk was found in Asian populations under allelic and dominant model(A vs G: OR = 1.93, 95% CI:1.51–2.48, P<0.00001; GA + AA vs GG: OR = 2.56, 95% CI:1.83–3.58, P<0.00001).
IL-4 -590C/T polymorphism and pediatric asthma risk
12 case-control studies including 2532 patients and 2827 controls were investigated. A significant association between IL-4 -590C/T polymorphism and pediatric asthma risk was shown under the homozygous model (TT vs CC: OR = 1.55, 95% CI:1.08–2.22, P = 0.02), heterozygous model (CT vs CC: OR = 1.29, 95% CI:1.06–1.56, P = 0.01), dominant model (CT + TT vs CC: OR = 1.44, 95% CI:1.06–1.95, P = 0.02) and recessive model (TT vs CT + CC: OR = 1.28, 95% CI:1.05–1.55, P = 0.01). Subgroup analysis showed that significant associations of IL-4 -590C/T polymorphism with asthma risks among Chinese children in the dominant model (CT + TT vs CC: OR = 1.79, 95% CI:1.38–2.33, P<0.0001). No association was found in Asian populations. Figure 2 showed forest plots of the association between the IL-4 -590C/T polymorphism and asthma risk. The results of sensitivity analysis found that a study (Dixit 2014) had a great impact on heterogeneity. After omitting this study, the between-study heterogeneity effectively decreased and fixed-effects model was applied: homozygous model (TT vs CC: OR = 1.85, 95% CI:1.44–2.37, P<0.00001, I2 = 9%), heterozygous model (CT vs CC: OR = 1.49, 95% CI:1.21–1.85, P = 0.0002, I2 = 0%), dominant model (CT + TT vs CC: OR = 1.64, 95% CI:1.34-2.00, P<0.00001, I2 = 8%). Other models have not changed significantly. We discovered that there is no directional change in the results after omitting this study, indicating that our results are statistically stable.
ADAM33 F + 1 polymorphism and pediatric asthma risk
We analyzed 1340 cases and 959 controls from five case-control studies. Combined data revealed that the TC + TT genotypes of ADAM33 F + 1 polymorphism was associated with an increased risk of pediatric asthma (TC + TT vs CC: OR = 1.24, 95% CI:1.04–1.48, P = 0.02) and revealed no statistically significant link between ADAM33 F + 1 polymorphism and the risk of childhood asthma in the allelic model(T vs C: OR = 1.33, 95% CI:0.99–1.79, P = 0.06), homozygous model(TT vs CC: OR = 1.81, 95% CI:0.95–3.44, P = 0.07), heterozygous model (TC vs CC: OR = 1.13, 95% CI:0.93–1.36, P = 0. 21)and recessive model (TT vs TC + CC: OR = 1.67, 95% CI:0.94–2.97, P = 0.08). No association was found between ADAM33 F + 1 polymorphism and pediatric asthma risk among Asian populations. Sensitivity analysis showed these results are instable. F + 1 was significantly associated with childhood asthma after omitting one study (Qu2011)34: allelic model (T vs C: OR = 1.48, 95% CI:1.14–1.92, P = 0.003), homozygous model (TT vs CC: OR = 2.34, 95% CI:1.40–3.92, P = 0.001), dominant model (TC + TT vs CC: OR = 1.43, 95% CI: 1.13–1.80, P = 0.003), recessive model (TT vs TC + CC: OR = 2.31, 95% CI:1.74–3.07, P<0.00001).
ADAM33 T2 polymorphism and pediatric asthma risk
Four studies containing 928 cases and 967 controls were synthesized. The result indicated that an increased risk of childhood asthma was observed in all the four models of ADAM33 T2 polymorphism: allelic model (A vs G: OR = 1.86, 95% CI:1.10–3.15, P = 0.02), homozygous model (AA vs GG: OR = 4.25, 95% CI:2.27–7.98, P<0.00001), heterozygous model (AG vs GG: OR = 1.71, 95% CI:1.03–2.85, P = 0.04), dominant model (AG + AA vs GG: OR = 1.87, 95% CI:1.07–3.27, P = 0.03), recessive model (AA vs GA + GG: OR = 3.72, 95% CI:1.98–6.98, P<0.0001). Subgroup analysis showed that the allele A and AG + AA genotype was associated with increased asthma risk in Asian populations (A vs G: OR = 2.26, 95% CI:1.29–3.94, P = 0.004; AG + AA vs GG: OR = 2.29, 95% CI:1.25–4.17, P = 0.007).
ADAM33 T1 polymorphism and pediatric asthma risk
4 case-control studies included 938 cases 928 controls. Compared with AA genotype, GG, GA and GA + GG genotype increased the susceptibility to asthma (GG vs AA: OR = 4.11, 95% CI:2.56–5.90, P<0.00001; GA vs AA: OR = 2.05, 95% CI:1.37–3.08, P = 0.0005; GA + GG vs AA: OR = 2.12, 95% CI:1.29–3.47, P = 0.003). No association between gene polymorphism and asthma risk was found in allelic and recessive models. The results of subgroup analysis showed that GA + GG genotype may increase the risk of childhood asthma in Asian populations (GA + GG vs AA : OR = 2.92, 95% CI: 2.35–3.63, P<0.00001).
ADAM33 ST + 4 polymorphism and pediatric asthma risk
When three studies containing 716 cases and 435 controls on ADAM33 ST + 4 polymorphism were combined, the analysis showed that the correlation between ADAM33 ST + 4 polymorphism and pediatric asthma risk was statistically significant in all genetic models under fixed-effects model: allelic model (G vs A: OR = 1.57, 95% CI:1.32–1.87, P<0.00001), homozygous model (CC vs AA: OR = 2.19, 95% CI:1.55–3.12, P<0.0001), heterozygous model (AC vs AA: OR = 1.59, 95% CI:1.18–2.13, P = 0.002), dominant model (AC + CC vs AA: OR = 1.81, 95% CI:1.37–2.39, P<0.0001), recessive model (CC vs AC + AA: OR = 1.74, 95% CI:1.31–2.30, P = 0.0001).
ORMDL3 rs7216389 polymorphism and pediatric asthma risk
We synthesized three studies including 448 cases and 478 controls. The results revealed that ORMDL3 rs7216389 polymorphism was associated with a high risk of childhood asthma in all four genetic model: allelic model (T vs C: OR = 1.81, 95% CI: 1.45–2.25, P<0.00001), homozygous model (TT vs CC: OR = 3.35, 95% CI: 1.24–7.57, P<0.00001), heterozygous model (TC vs CC: OR = 1.98, 95% CI: 1.11–3.56, P = 0.02), dominant model (TC + TT vs CC: OR = 2.76, 95% CI:1.58–4.82, P = 0.0004), recessive model (TT vs TC + CC: OR = 1.89, 95% CI: 1.44–2.47, P<0.00001).
VDR ApaⅠ polymorphism and pediatric asthma risk
Five studies included 426 cases and 476 controls. Our analysis suggested that VDR ApaⅠ polymorphism were associated with high pediatric risk under allelic(C vs A: OR = 1.31, 95% CI:1.06–1.62, P = 0.01), homozygous ( CC vs AA: OR = 1.94, 95% CI:1.17–3.24, P = 0.01), heterozygous (AC T vs AA: OR = 2.18, 95% CI:1.34–3.56, P = 0.002) and dominant model (AC + CC vs AA: OR = 1.95, 95% CI:1.26–3.01, P = 0.003). Subgroup analysis showed that the allele C was associated with increased asthma risk in Asians population (C vs A: OR = 1.60, 95% CI:1.13–2.27, P = 0.008).
VDR FokⅠ polymorphism and pediatric asthma risk
Six studies included 503 cases and 465 controls. Results revealed that VDR FokⅠ polymorphism was associated with increased risk of childhood asthma in dominant model (TC + TT vs CC: OR = 1.39, 95% CI:1.02–1.89, P = 0.04) and recessive model (TT vs TC + CC: OR = 1.50, 95% CI:1.12–2.01, P = 0.006) under fixed-effects model. No association was found in other models. Subgroup analysis did not find a significant relationship in Asians.
VDR BsmⅠ polymorphism and pediatric asthma risk
Five studies included 430 cases and 496 controls. Our result found VDR BsmⅠ polymorphism were associated with increased the risk of asthma under four genetic comparison models: allelic model (A vs G: OR = 1.47, 95% CI:1.15–1.88, P = 0.002), homozygous model (AA vs GG: OR = 1.79, 95% CI:1.03–3.11, P = 0.04), heterozygous model (AG vs GG: OR = 1.91, 95% CI:1.02–3.58, P = 0.04), dominant model (AG + AA vs GG: OR = 1.74, 95% CI:1.05–2.88, P = 0.03) and recessive model (AA vs AG + GG: OR = 1.61, 95% CI:1.16–2.25, P = 0.005). Subgroup analysis showed VDR BsmⅠ polymorphism was related with childhood asthma in Asian populations (A vs G: OR = 1.81, 95% CI:1.15–2.85, P = 0.01; AG + AA vs GG: OR = 2.26, 95% CI:1.34–3.82, P = 0.002).
No association between other 8 gene polymorphism (IL-13 -1112C/T, IL-13 + 1923 C/T, ADRB2 -46 G /A, ADRB2 -79G/C, ADAM33 V4, ADAM33 S2, CTLA-4 + 49 A /G, VDR TaqⅠ) and susceptibility to pediatric asthma was found in total population and in Asians.