Table 4.
Determinants of nicotine disposition kinetics
| Gene SNP/Variant | Alleles | MAF | P-Value% | Variance explained |
|---|---|---|---|---|
| Nicotine half-life | ||||
| 3HC/COT (d0) 360 min | p<0.0001 | 37.2% | ||
| UGT2B10 rs116294140 | A:C | 0.38 | 0.09 | 2.9% |
| UGT2B10 rs61750900 | G:T | 0.03 | 0.38 | 0.8% |
| FMO3 rs2266782 | G:A | 0.39 | 0.29 | 1.1% |
| OCT2 rs316019 | C:A | 0.07 | 0.54 | 0.4% |
| Nicotine Cmax | ||||
| 3HC/COT (d0) 360 min | 0.84 | 0.1% | ||
| UGT2B10 rs116294140 | A:C | 0.38 | 0.35 | 1.3% |
| UGT2B10 rs61750900 | G:T | 0.03 | 0.68 | 0.3% |
| FMO3 rs2266782 | G:A | 0.39 | 0.97 | 0.0% |
| OCT2 rs316019 | C:A | 0.07 | 0.001 | 18.0% |
| Nicotine AUC | ||||
| 3HC/COT (d0) 360 min | 0.005 | 12.5% | ||
| UGT2B10 rs116294140 | A:C | 0.38 | 0.34 | 1.4% |
| UGT2B10 rs61750900 | G:T | 0.03 | 0.74 | 0.2% |
| FMO3 rs2266782 | G:A | 0.39 | 0.70 | 0.2% |
| OCT2 rs316019 | C:A | 0.07 | 0.01 | 9.4% |
| Nicotine non-renal CL | ||||
| 3HC/COT (d0) 360 min | 0.003 | 13.5% | ||
| UGT2B10 rs116294140 | A:C | 0.38 | 0.09 | 4.2% |
| UGT2B10 rs61750900 | G:T | 0.03 | 0.99 | 0.0% |
| FMO3 rs2266782 | G:A | 0.39 | 0.97 | 0.0% |
| OCT2 rs316019 | C:A | 0.07 | 0.01 | 8.8% |
| Nicotine total CL | ||||
| 3HC/COT (d0) 360 min | 0.002 | 14.1% | ||
| UGT2B10 rs116294140 | A:C | 0.38 | 0.09 | 4.0% |
| UGT2B10 rs61750900 | G:T | 0.03 | 0.93 | 0.0% |
| FMO3 rs2266782 | G:A | 0.39 | 0.98 | 0.0% |
| OCT2 rs316019 | C:A | 0.07 | 0.01 | 9.1% |
Alleles indicated as major:minor with impaired allele in bolded italics. P-value and percentage of variance in the pharmacokinetic parameters explained by the variables are from standard multiple regression modelling assuming a dominant effect of the minor. % Variance explained is calculated based on the square value of the part correlation coefficients. Abbreviation: MAF, minor allele frequency; CL, clearance.