Table 5.

Determinants of cotinine disposition kinetics

Gene SNP/Variant	Alleles	MAF	P-Value	% Variance explained
Cotinine half-life
3HC/COT (d0) 360 min			p<0.0001	30.9%
UGT2B10 rs116294140	A:C	0.38	0.78	0.1%
UGT2B10 rs61750900	G:T	0.03	0.76	0.1%
UGT2B17*2	1:0	0.32	0.33	1.2%
FMO3 rs2266782	G:A	0.39	0.42	0.8%
OCT2 rs316019	C:A	0.07	0.48	0.6%
Cotinine Cmax
3HC/COT (d0) 360 min			0.22	2.6%
UGT2B10 rs116294140	A:C	0.38	0.80	0.1%
UGT2B10 rs61750900	G:T	0.03	0.95	0.0%
UGT2B17*2	1:0	0.32	0.72	0.2%
FMO3 rs2266782	G:A	0.39	0.30	1.8%
OCT2 rs316019	C:A	0.07	0.02	9.4%
Cotinine AUC
3HC/COT (d0) 360 min			p<0.0001	24.0%
UGT2B10 rs116294140	A:C	0.38	p<0.0001	13.8%
UGT2B10 rs61750900	G:T	0.03	0.13	2.2%
UGT2B17*2	1:0	0.32	0.06	3.5%
FMO3 rs2266782	G:A	0.39	0.06	3.5%
OCT2 rs316019	C:A	0.07	0.45	0.5%
Cotinine non-renal CL
3HC/COT (d0) 360 min			p<0.0001	35.9%
UGT2B10 rs116294140	A:C	0.38	0.001	10.7%
UGT2B10 rs61750900	G:T	0.03	0.17	1.6%
UGT2B17*2	1:0	0.32	0.24	1.2%
FMO3 rs2266782	G:A	0.39	0.74	0.1%
OCT2 rs316019	C:A	0.07	0.45	0.5%
Cotinine total CL
3HC/COT (d0) 360 min			p<0.0001	35.6%
UGT2B10 rs116294140	A:C	0.38	p<0.0001	12.7%
UGT2B10 rs61750900	G:T	0.03	0.05	3.0%
UGT2B17*2	1:0	0.32	0.02	4.3%
FMO3 rs2266782	G:A	0.39	0.36	0.7%
OCT2 rs316019	C:A	0.07	0.18	1.3%

UGT2B17 0 allele: deletion allele. 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 allele. % Variance explained is calculated based on the square value of the part correlation coefficients. Abbreviation: MAF, minor allele frequency; CL, clearance.