TABLE 2

Successful examples of the application of quantitative proteomics for the characterization of interindividual variability in DMET abundance

Enzyme/TransporterFold Change
Reference
Effect of age (liver): fold change (relative to infants)
CYP1A2>2-fold (adults); >1- to 2-fold (juveniles)Sadler et al., 2016
CYP2A6>2-fold (adults)
CYP2B6>2-fold (juveniles)
CYP3A5>2-fold (juveniles, adults)
UGT1A1>1- to 2-fold (adults)
Bhatt et al., 2019
UGT1A4>2-fold (children, adolescents, adults)
UGT1A6>2-fold (children, adolescents, adults)
UGT1A9>2-fold (adults)
UGT2B7>2-fold (adolescents, adults)
UGT2B15>2-fold (adults)
UGT2B17>2-fold (children, adolescents, adults);Bhatt et al., 2018
ALDH1A1>1- to 2-fold (children, adolescents)Bhatt et al., 2017
ADH1B>2-fold (children); >1- to 2-fold (adolescents, adults)
ADH1C>2-fold (children, adolescents, adults)

CES1

>2-fold (adults); >1- to 2-fold (children, adolescents)

Boberg et al., 2017

FMO3

>1- to 2-fold (children, adult)

Zane et al., 2018
SULT1A1>1- to 2-fold (children)Ladumor et al., 2019a
SULT1A2>1-- to 2-fold (adolescents, adults)Dubaisi et al., 2019
SULT1B1>2-fold (infants, children, adolescents, adults)Ladumor et al., 2019a)

OCT1

>1- to 2-fold (adolescents, adults)

Prasad et al., 2016; van Groen et al., 2018

OATP1B3

>1- to 2-fold (children, adolescents, adults)

Prasad et al., 2016; van Groen et al., 2018
P-gp>1- to 2-fold (adolescents, adults)Prasad et al., 2016; van Groen et al., 2018

MRP3

>1- to 2-fold (adult)

Prasad et al., 2016; van Groen et al., 2018
Effect of age (kidney): fold change (relative to infants)
P-gp>1- to 2-fold (children, adults)Cheung et al., 2019
URAT1>2-fold (children)
OAT1>1- to 2-fold (children, adults)
OAT3>1- to 2-fold (children, adolescents, adults)
OCT2>1- to 2-fold (children)
Effect of genotype: fold change (relative to the corresponding reference allele)
BCRP<0.5-fold (rs2231142 (C421A))Prasad et al., 2013
MRP2>1- to 2-fold (SNP 21214G>A (V417I)Deo et al., 2012
OATP1B1>2-fold (SNP c.463C>A); >1- to 2-fold (388 A>G, c.597C>T)Prasad et al., 2014
CYP2A6
>1- to 2-fold (*1/*4, ↑ *1/*9); <1–0.5-fold (*1/*17, *1/*2)

Tanner et al., 2017; Tanner et al., 2018
FMO3>1- to 2-fold (E158K:G308G)Xu et al., 2017

UGT2B17
>1- to 2-fold (*1/*2); < 0.5-fold (*2/*2)Gaedigk et al., 2018
Effect of sex: fold change (male versus female adults)
BCRP>1- to 2-foldPrasad et al., 2013
UGT2B17>2-foldTanner et al., 2017
CYP2A6<1- to 2-fold
FMO3>1- to 2-foldXu et al., 2017
Effect of disease condition: fold change (relative to healthy adults)
Alcoholic liver disease (CPS A)>2-fold (P-gp); < 0.5-fold (BSEP, MRP2, OAT2, OATP1B1, OATP2B1)Wang et al., 2016; Drozdzik et al., 2020
Alcoholic liver disease (CPS B)>2-fold (P-gp); <0.5-fold (BSEP, MRP2, NTCP, OCT1, OCT3, OAT2, OATP1B1, OATP1B3, OATP2B1)Drozdzik et al., 2020
Alcoholic liver disease (CPS C)>2-fold (P-gp, MRP3, BCRP, OCT3); <0.5-fold (MRP2, NTCP, OAT2, OATP1B1, OATP2B1)Drozdzik et al., 2020
Nonalcoholic fatty liver disease<0.5-fold (CYP3A4)Ali et al., 2017
Nonalcoholic steatohepatitis>2-fold (OATP1B1, MRP4); <0.5-fold (NTCP, OATP1B3)
HCV>2-fold (MRP3, MRP4, P-gp); <0.5-fold (CYP3A4, CYP2C9, CYP2E1, CYP1A2, CYP2A6, CYP2C8, UGT1A4, UGT1A6, UGT2B7, UGT2B15, CES1, ADH1B, ADH1C)Wang et al., 2016
HCV (CPS A)>2-fold (P-gp); <0.5-fold (BSEP, MRP1, MRP2, BCRP, NTCP, OCT1, OCT3, OATP1B1, OATP2B1)Drozdzik et al., 2020
HCV (CPS B)>2-fold (P-gp, MRP1); <0.5-fold (BSEP, MRP2, OCT1, OCT3, OATP1B3, OATP2B1)
HCV (CPS C)>2-fold (P-gp, MRP3); <0.5-fold (BSEP, MRP1, NTCP, OCT1, OCT3, OATP1B3, OATP2B1)
Primary biliary cirrhosis; PSC (CPS A)>2-fold (P-gp, BSEP, MRP3, OCT3, OATP1B3); <0.5-fold (MRP2)
PSC (CPS B)>2-fold (P-gp, MRP3, OCT3); <0.5-fold (MRP2, OATP1B3)
Autoimmune hepatitis (AIH) (CPS A)>2-fold (P-gp, MRP3, BCRP, OCT3); <0.5-fold (MRP1, MRP2)
AIH (CPS B)>2-fold (P-gp, MRP3, BCRP, OCT3); <0.5-fold (MRP2)

AIH (CPS C)
>2-fold (P-gp, MRP3, OCT3); <0.5-fold (MRP2, NTCP, OCT1, OATP1B1)
Ulcerative colitis<0.5-fold (MCT1)Erdmann et al., 2019