Common single nucleotide polymorphism in DMET proteins that affect their activity or abundance

ProteinNucleotide Change; Allele; Amino Acid Change (rs Number)MAF (Caucasians, %)Activity (Abundance)Clinical ApplicationReferences
CYP1A13801 T>C; *2A; I462V (rs4646903)19Increased (unknown)Predictor for clinical outcome in liver cancer patients treated with EGFR-TKI therapyZhou et al., 2009
CYP1A2−163C>A; *1F; NA (rs762551)33.3Increased (increased)Associated with the risk for colorectal adenomas in humansSachse et al., 2003; Moonen et al., 2005; Pilgrim et al., 2012
−246T>delT; *1D; NA4.82Decreased (decreased)Higher olanzapine plasma concentrationSachse et al., 2003; Uslu et al., 2010; Czerwensky et al., 2015
CYP2C9430 C>T; *2; R144C (rs1799853)19.0% *1/*2 1.6% *2/*2 1.8% *2/*3Decreased (unknown)Poor warfarin metabolismAithal et al., 1999; Hillman et al., 2004; Lindh et al., 2009
1075A>C; *3; I359L (rs1057910)9Decreased (unknown)Decrease metabolism of phenytoin compared with reference genotypeScordo et al., 2001; van der Weide et al., 2001; Rosemary et al., 2006
CYP2C19681G>A; *2; splicing variant I331V
16Decreased (unknown)In Asians with ulcer treatment of Helicobacter pylori infection with omeprazole varying treatment effectivenessAynacioglu et al., 1999
−806C>T and -3402C>T; *17; I331V (rs12248560)18Increased (increased)Increase clinical response to clopidogrel treatment by better antiplatelet activity and higher risk of bleedingSibbing et al., 2010; Santos et al., 2011
CYP2D61749A>G, 2549delA; *3; frameshift mutation, N166D; 259 (rs1135824)2.04Decreased (decreased)Decreased metabolism of risperidoneSachse et al., 1997
1846G>A; *4; P34S; L91M; H94R; Splicing variant; S486T (rs3892097)20.7Decreased (decreased)Poor metabolism of tricyclic antidepressants may lead to increased toxicity in CaucasiansSachse et al., 1997; Bijl et al., 2008
100C>T; 1039C>T; 1661G>C; 1846G>A; 4180G>C; *4D; P34S; Splicing variant; S486T (NA)3.4Decreased (decreased)Shimada et al., 2001
100C>T; 997C>G; 1661G>C; 1846G>A; 4180G>C; *4L; P34S; Splicing variant; S486T (NA)4.5Decreased (decreased)Shimada et al., 2001
whole gene deletion; *5; CYP2D6 deleted (NA)4.1Deletion (deleted)Require dose adjustment of CYP2D6 substratesGriese et al., 1998
1707delT; *6; frameshift mutation, 118F (rs5030655)1.3Nonfunctional (decreased)Person may experience haloperidol-induced extrapyramidal side effectsGriese et al., 1998; Šimić et al., 2016)
2935A>C; *7; H324 (rs5030867)1Decreased (unknown)Evert et al., 1997
2615-2617delAAG; *9; K281del (rs5030656)2Decreased (unknown)Griese et al., 1998
100C>T; *10; P34S; S486T (rs1065852)8Decreased (unknown)Griese et al., 1998; Raimundo et al., 2004
2988G>A; *41; R296C; Splicing variant; S486T (rs28371725)8Decreased (decreased)Raimundo et al., 2004
CYP2A6NA; *12; substitutions 10aa (esv2663194)2.9Decreased (unknown)Haberl et al., 2005
NA; *1B; NA;NA32.6Increased (unknown)Faster nicotine metabolismMwenifumbo et al., 2008; Djordjevic et al., 2013
1799 T > A; *2; L160 (rs1801272)2.3Decreased (unknown)Shifting of coumarin metabolism from 7-OH coumarin to 2-hydroxyphenylacetic acidHadidi et al., 1997; Ingelman-Sundberg, 2001
NA; *4; deletionDeletion (deleted)Impairment of nicotine metabolismIngelman-Sundberg, 2001
− 48 T > G; *9; TATA box (rs28399433)7.1Decreased (decreased)Schoedel et al., 2004
CYP3A4566T>C; *17; F189S (rs4987161)Decreased (unknown)Decreased metabolism of nifedipineDai et al., 2001
NA; *1B; NA (rs2740574)17Increased (unknown)Higher docetaxel metabolismKadlubar et al., 2003; Tran et al., 2006
664T>C; *2; S222P (rs5585340)2.7Decreased (unknown)Sata et al., 2000
CYP3A56986A>G; *3C; Splicing defect (rs776746)81.3Decreased (decreased)Prognosis of non–small cell lung cancer patients undergoing chemotherapy and surgeryQuaranta et al., 2006; Jiang et al., 2016
6981A>G, 29748T>C; *3k / *10; Splicing defect; F446S (rs41279854)

Decreased (decreased)

Lee et al., 2003
CYP2B664C>T; *2; R22C; rs81927095.3Increased (unknown)Hiratsuka et al., 2002; Honda et al., 2011
1459C>T; *5; R487C (rs3211371)14.0Decreased (unknown)Decreased S-mephenytoin N-demethylase activityLang et al., 2001
785A>G; *4; K262R (rs4802101)5.0Increased (unknown)Lang et al., 2001; Kirchheiner et al., 2003

516G>T, 785A>G; *6; Q172H; K262R (rs3745274, rs2279343)
25.2Decreased (unknown)Lang et al., 2001; Kirchheiner et al., 2003

−1456T>C, -750T>C, .785A>G, 1459C>T; *7; Q172H; K262R; R487C (rs3745274, rs2279343, rs3211371)
Decreased (unknown)Decreased S-mephenytoin N-demethylase activityHiratsuka et al., 2002; Lamba et al., 2003
Gene deletion, *2; NA (rs10025771)Decreased (decreased)Bhatt et al., 2018
UGT2B17−155G>A,840A>T, 788G>T, 2603T>G; H2/H2; NA (rs7436962, rs9996186, rs4860305, and rs28374627)22IncreasedBhatt et al., 2018
UGT1A1NA; *28; TATA box (rs8175347)2631Decreased (decreased)
Decreased glucuronidation of bilirubin to about 30% of wild-type levels, adverse
reactions to irinotecan treatment
Bosma et al., 1995; Marques and Ikediobi, 2010
SULT2A1187G>C, 679A>G, 781G>A; NA; A63P, K227D and A261T (rs6639786, rs2270112, and rs17268988)Decreased (NA)Decreased metabolism of tiboloneThomae et al., 2002; Miller et al., 2018; Wong et al., 2018
GSTP1313A>G; NA; I105V (rs1695)0.080.33Decreased (unknown)Alters the pharmacokinetics of cyclophosphamideSharma et al., 2014
UGT2B7802C>T; *2; H268Y (rs7439366)50Decreased (NA)Higher exposure of epirubicinBhasker et al., 2000; Parmar et al., 2011; Uchaipichat et al., 2013
UGT2B15253G>T; *2; D85Y (NA)50Decreased (NA)Interindividual variability in the clearance of oxazepam and lorazepam
BCRP421C>A; NA; Q41K (rs2231342)4.512Decreased (decreased)AUC of sulfasalazine, simvastatin, and rosuvastatin >2-fold higher in comparison with reference allelePrasad et al., 2013; Tanaka et al., 2015
OATP2B1388A>G, 521T>C and 388A>G; c.521T>C, Asn130Asp; p.Val174Ala; *1b, *5, and *15; N130D, V174A, (rs2306283, rs2306283)30, 16 and 14Decreased (NA)Interindividual variability in statin therapyGao et al., 2017; Mori et al., 2019
OATP1B1463C>A; *14; R155C (rs149535236)2Increased (increased)Cerivastatin-induced rhabdomyolysisCouvert et al., 2008; Romaine et al., 2010; Tamraz et al., 2013
OCT1181C>T, 1201G>A, 1393G>A, 1257delATG; *2, *3, *4, *5; R61C, G401S, G465R and deletion of M420 (rs12208357, rs34130495, rs34059508, rs35167514)9, 3, 16Decreased (NA)Impaired metformin uptake and lower morphine clearance in pediatricsSaadatmand et al., 2012; Fukuda et al., 2013; Arimany-Nardi et al., 2015
OCT2808G>T; NA; A270S (rs316019)NA (NA)Meyer et al., 2017)