Table 5. Subgroup analysis of the CYP3A4*1B genetic polymorphism on weight adjusted tacrolimus daily dose (Dose) and C0/Dose by time of post-transplantation in European (Indian population removed).
| Subgroup(CYP3A4*1/*1 vs. CYP3A4*1B carriers) | Studies included (observations) | WMD(95% CI) | P | I 2(%) | SMD(95% CI) | P | I 2(%) |
|---|---|---|---|---|---|---|---|
| Dose | |||||||
| By time of PT c | |||||||
| 7 days | 19–22,24(5) | -0.048(-0.083,-0.014) | 0.006 | 78.2 | -0.781(-1.281,-0.281) | 0.002 | 69.5 |
| 1 month | 19,21(2) | -0.023(-0.045,-0.000) | 0.047 | 0.0 | -0.274(-0.727,0.179) | 0.235 | 0.0 |
| 3 months | 19,24,25(3) | -0.065(-0.119,0.010) | 0.021 | 70.4 | -1.231(-2.188,-0.273) | 0.012 | 83.0 |
| 6 months | 19–22,24(5) | -0.058(-0.081,-0.036) | <0.001 | 43.4 | -1.033(-1.465,-0.601) | <0.001 | 58.6 |
| 12 months | 19,21,22,24,25(5) | -0.061(-0.096,-0.027) | 0.001 | 79.3 | -1.241(-1.973,-0.508) | 0.001 | 84.2 |
| By CYP3A5 & time of PT c | |||||||
| CYP3A5*3/*3 | |||||||
| 7 days | 20,22(2) | -0.031(-0.059,-0.003) | 0.033 | 13.2 | -0.444(-0.818,-0.071) | 0.020 | 0.0 |
| 6 months | 20,22(2) | -0.037(-0.050,-0.024) | <0.001 | 0.0 | -0.604(-1.005,-0.204) | 0.003 | 10.6 |
| 12 months | 22(1) a | -0.040(-0.064,-0.016) | 0.001 | NA | -0.278(-0.908,0.352) | 0.388 | NA |
| CYP3A5*1 carriers | |||||||
| 7 days | 20–22,24(4) | -0.059(-0.141,0.022) | 0.154 | 88.7 | -0.793(-1.800,0.215) | 0.123 | 76.9 |
| 1 month | 21(1) a | 0.020(-0.024,0.064) | 0.371 | NA | 0.566(-0.705,1.836) | 0.383 | NA |
| 3 months | 24(1) a | -0.030(-0.145,0.085) | 0.608 | NA | -0.272(-1.292,0.748) | 0.601 | NA |
| 6 months | 20–22,24(4) | -0.032(-0.059,-0.004) | 0.025 | 1.7 | -0.622(-1.054,-0.190) | 0.005 | 0.0 |
| 12 months | 21,22,24(3) | -0.050(-0.092,-0.008) | 0.020 | 47.7 | -0.991(-1.557,-0.424) | 0.001 | 17.2 |
| C 0 /Dose | |||||||
| By time of PT c | |||||||
| 7 days | 19-22(4) | 19.971(-7.707,47.650) | 0.157 | 81.1 | 0.189(-0.156,0.533) | 0.283 | 26.6 |
| 1 month | 19,21(2) | 58.129(40.584,75.675) | <0.001 | 0.0 | 0.643(0.176,1.109) | 0.007 | 3.0 |
| 3 months | 19,25(2) | 14.790(-15.089,44.668) | 0.332 | 0.0 | 0.244(-0.170,0.658) | 0.247 | 0.0 |
| 6 months | 19-22(4) | 52.588(22.387,82.789) | 0.001 | 59.1 | 0.344(-0.026,0.715) | 0.069 | 41.6 |
| 12 months | 19,21,22,25(4) | 62.219(14.218,110.221) | 0.011 | 86.5 | 0.350(0.037,0.663) | 0.028 | 14.0 |
| By CYP3A5 & time of PT c | |||||||
| CYP3A5*3/*3 | |||||||
| 7 days | 19,20,22(3) | -5.800(-17.709,6.109) | 0.340 | 0.0 | -0.075(-0.490,0.340) | 0.723 | 0.0 |
| 1 month | 19(1) a | 25.100(-8.015,58.215) | 0.137 | NA | 0.225(-0.586,1.036) | 0.587 | NA |
| 3 months | 19(1) a | -37.400(-178.178,103.378) | 0.603 | NA | -0.376(-1.188,0.435) | 0.364 | NA |
| 6 months | 19,20,22(3) | 49.715(6.896,92.533) | 0.023 | 54.0 | 0.192(-0.224,0.607) | 0.366 | 0.0 |
| 12 months | 19,22(2) | 21.241(-72.999,115.480) | 0.659 | 72.0 | 0.028(-0.495,0.551) | 0.918 | 8.5 |
| CYP3A5*1 carriers b | |||||||
| 7 days | 19–22,24(5) | NA | NA | NA | 0.365(-0.021,0.750) | 0.064 | 0.0 |
| 1 month | 19,21(2) | NA | NA | NA | 0.222(-0.523,0.966) | 0.559 | 0.0 |
| 3 months | 19,24(2) | NA | NA | NA | 0.323(-0.369,1.015) | 0.360 | 0.0 |
| 6 months | 19–22,24(5) | NA | NA | NA | 0.142(-0.390,0.674) | 0.601 | 36.3 |
| 12 months | 19,21,22,24(4) | NA | NA | NA | 0.619(-0.031,1.269) | 0.062 | 45.7 |
NA: not available.
a only one observation.
b the units of C0/Dose are different, so the data were pooled by SMD;
c PT: post-transplantation.