Table 5.
The impact of genotype on the relationship between loop diuretics or proton pump inhibitors and the endpoints
| Loop diuretic | Proton pump inhibitor | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ABCG2 rs2231142 (C421A, Q141K) | Interaction P‐value | CYP2C19 | Interaction P‐value | |||||||||
| WT (n = 435) | Variant carrier (n = 136) | PM/IM (n = 152) | EM (n = 233) | RM/UM (n = 186) | ||||||||
| On LD (n = 74) | On LD (n = 22) | On PPI (n = 58) | On PPI (n = 88) | On PPI (n = 83) | ||||||||
| B (SE) | P‐value | B (SE) | P‐value | B (SE) | P‐value | B (SE) | P‐value | B (SE) | P‐value | |||
| ATV | 0.121 (0.044) | .0066 | 0.041 (0.086) | .63 | .52 | 0.046 (0.061) | .46 | 0.052 (0.045) | .25 | 0.162 (0.050) | .0015 | .078 |
| 2‐OH ATV | 0.072 (0.039) | .068 | −0.051 (0.077) | .51 | .22 | 0.032 (0.050) | .52 | 0.045 (0.038) | .24 | 0.191 (0.042) | .0050 | .16 |
| ATV L | 0.149 (0.048) | .0022 | 0.077 (0.089) | .38 | .54 | 0.084 (0.070) | .23 | 0.076 (0.050) | .13 | 0.232 (0.053) | .000018 | .025 |
| 2‐OH ATV L | 0.102 (0.040) | .011 | 0.044 (0.075) | .55 | .52 | 0.018 (0.057) | .75 | 0.065 (0.039) | .094 | 0.199 (0.042) | 5.28x10–6 | .0071 |
| 2‐OH ATV/ATV | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| 2‐OH ATV L/ATV L | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ | ‐ |
| ATV L/ATV | ‐ | ‐ | ‐ | ‐ | ‐ | 0.022 (0.040) | .59 | 0.021 (0.036) | .49 | 0.069 (0.031) | .047 | .24 |
| TOTAL | 0.120 (0.036) | .00088 | 0.013 (0.069) | .85 | .31 | 0.033 (0.051) | .52 | 0.060 (0.036) | .094 | 0.162 (0.039) | .000060 | .031 |
Analysis was conducted limited to those endpoints for which loop diuretic or PPI had been included in the main analysis multivariable model. CYP2C19 poor and intermediate metabolisers were grouped together because there were only 10 patients with the poor metaboliser (*2/*2) genotype, and CYP2C19 rapid and ultra‐rapid metabolisers were combined as there were only 24 ultra‐rapid metabolisers (*17/*17). The genotype groups for CYP2C19 considered in interaction testing were rapid/ultra‐rapid metaboliser (RM/UM) vs non‐RM/UM.