Table II.
UGT 2B10 genotype | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Asp67Tyr variant (rs6175900) | Splice variant (rs116294140) | Both variants | |||||||||
Alla | Alla | AAs | All | ||||||||
N | Means (95% CI) | N | Means (95% CI) | N | Means (95% CI) | Genetic scoreb | N | Means (95% CI) | |||
Nicotine metabolism pathways | |||||||||||
N-glucuronidation | |||||||||||
Nicotine glucuronide/TNE | GG | 2028 | 0.039 (0.037–0.042) | AA | 1853 | 0.042 (0.038–0.045) | 156 | 0.03 (0.024–0.039) | 0 | 1664 | 0.047 (0.043–0.051) |
GT | 204 | 0.014 (0.01–0.021) | CA | 333 | 0.025 (0.016–0.04) | 166 | 0.02 (0.013–0.02) | 1 | 503 | 0.021 (0.018–0.024) | |
TTc | 2 | 0.000 | CCc | 48 | 0.002 (0.001–0.003) | 41 | 0.00 (0.001–0.003) | 2c | 67 | 0.000 (0-0) | |
P-value | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||||
N-oxidation | |||||||||||
Nicotine N-oxide/TNE | GG | 2032 | 0.054 (0.052–0.056) | AA | 1858 | 0.053 (0.051–0.055) | 157 | 0.052 (0.046–0.058) | 0 | 1668 | 0.054 (0.052–0.056) |
GT | 205 | 0.052 (0.044–0.061) | CA | 333 | 0.050 (0.041–0.063) | 166 | 0.050 (0.044–0.056) | 1 | 504 | 0.052 (0.048–0.055) | |
TTc | 2 | 0.043 (0.041–0.044) | CCc | 48 | 0.060 (0.049–0.075) | 41 | 0.056 (0.045–0.07) | 2c | 65 | 0.070 (0.046–0.106) | |
P-value | 0.5978 | 0.2584 | 0.6361 | 0.2553 | |||||||
C-oxidationd | |||||||||||
(Total 3-HCOT+total cotinine)/TNE | GG | 2032 | 0.726 (0.718–0.734) | AA | 1858 | 0.722 (0.713–0.73) | 157 | 0.757 (0.729–0.784) | 0 | 1668 | 0.720 (0.711–0.729) |
GT | 205 | 0.743 (0.703–0.782) | CA | 333 | 0.746 (0.695–0.797) | 166 | 0.792 (0.765–0.819) | 1 | 504 | 0.748 (0.731–0.764) | |
TTc | 2 | 0.913 (0.894–0.932) | CCc | 48 | 0.777 (0.727–0.828) | 41 | 0.826 (0.774–0.879) | 2c | 67 | 0.758 (0.66–0.856) | |
P-value | 0.4112 | 0.5023 | 0.0334 | 0.0116 | |||||||
Measures of enzyme activity | |||||||||||
UGT2B10 | |||||||||||
Nicotine glucuronide/ nicotine | GG | 2028 | 0.377 (0.344–0.414) | AA | 1853 | 0.39 (0.352–0.429) | 156 | 0.31 (0.225–0.421) | 0 | 1664 | 0.45 (0.402–0.496) |
GT | 204 | 0.126 (0.08–0.201) | CA | 333 | 0.23 (0.128–0.411) | 166 | 0.19 (0.143–0.264) | 1 | 503 | 0.19 (0.155–0.224) | |
TTc | 2 | 0.00 | CCc | 48 | 0.01 (0.008–0.027) | 41 | 0.02 (0.01–0.036) | 2c | 67 | 0.00 (0–0.001) | |
P-value | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||||
Cotinine glucuronide/ cotinine | GG | 2031 | 1.12 (1.07–1.17) | AA | 1857 | 1.28 (1.22–1.38) | 157 | 1.10 (0.97–1.24)b | 0 | 1668 | 1.38 (1.33–1.44) |
GT | 205 | 0.54 (0.43–0.68) | CA | 333 | 0.63 (0.5–0.80) | 166 | 0.48 (0.42–0.54) | 1 | 504 | 0.68 (0.63–0.73) | |
TTc | 1 | 0.01 | CCc | 47 | 0.02 (0.02–0.03) | 40 | 0.02 (0.02–0.03) | 2c | 65 | 0.01 (0.005–0.013) | |
P-value | <0.0001 | <0.0001 | <0.0001 | <0.0001 | |||||||
CYP2A6 | |||||||||||
Total 3-HCOT/total cotinine | GG | 2032 | 1.38 (1.34–1.43) | AA | 1858 | 1.33 (1.29–1.38) | 157 | 1.65 (1.469–1.853) | 0 | 1668 | 1.29 (1.24–1.34) |
GT | 205 | 1.84 (1.56–2.18) | CA | 333 | 1.63 (1.31–2.02) | 166 | 2.24 (2.003–2.513) | 1 | 504 | 1.78 (1.66–1.90) | |
TTc | 2 | 4.06 (2.82–5.30) | CCc | 48 | 3.76 (3.03–4.67) | 41 | 4.75 (3.794–5.952) | 2c | 67 | 3.09 (2.04–4.69) | |
P-value | 0.0011 | 0.0006 | <0.0001 | <0.0001 | |||||||
Total 3-HCOT/cotinine | GG | 2031 | 3.21 (3.10–3.32) | AA | 1857 | 3.23 (3.11–3.35) | 157 | 3.78 (3.35–4.26) | 0 | 1668 | 3.23 (3.10–3.37) |
GT | 205 | 3.35 (2.82–3.98) | CA | 333 | 2.90 (2.32–3.63) | 166 | 3.64 (3.23–4.09) | 1 | 504 | 3.19 (2.97–3.43) | |
TTc | 1 | 5.35 | CCc | 47 | 3.72 (2.97–4.66) | 40 | 4.52 (3.57–5.72) | 2c | 65 | 3.11 (2.01–4.81) | |
P-value | 0.631 | 0.6264 | 0.2706 | 0.9452 | |||||||
FMO3 | |||||||||||
Nicotine-N-oxide/nicotine | GG | 2028 | 0.54 (0.52–0.56) | AA | 1853 | 0.52 (0.50–0.54) | 156 | 0.55 (0.48–0.63) | 0 | 1664 | 0.53 (0.51–0.56) |
GT | 204 | 0.54 (0.45–0.65) | CA | 333 | 0.50 (0.39–0.64) | 166 | 0.67 (0.59–0.76) | 1 | 503 | 0.51 (0.47–0.55) | |
TTc | 2 | 1.03 (0.69–1.38) | CCc | 48 | 0.66 (0.52–0.85) | 41 | 0.77 (0.6–0.97) | 2c | 67 | 0.71 (0.44–1.14) | |
P-value | 0.933 | 0.7811 | 0.0235 | 0.287 |
aIncudes all five ethnic groups, values are adjusted for age, sex, creatinine (natural log), BMI (natural log), and race.
bGenetic score 0, rs61750900 GG and rs116294140 AA; score 1, rs61750900 GT or rs116294140 CA; score 2, rs61750900 TT or rs116294140 CC, or both rs61750900 GT and rs116294140 CA
cIf n < 10 the mean (minimum-maximum) are presented, not the geometric means and 95% CIs.
dArithmetic means are presented.