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Logo of bmcmedgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Medical Genomics
Published online 2008 June 11. doi: 10.1186/1755-8794-1-24

Table 1

Select examples of SNPs with clinical significance.

Phase I metabolism enzymes,
Allele nomenclature for Cytochrome P450 enzymes [24]:

CYP2C9rs1799853*2, R144CPM 0.25% in Caucasians, life-threatening bleeding after given warfarinNo

rs1057910*3, I359LYes

CYP2C19rs4244285*2, 681G>A, exon 5, splicing defectPM phenotype 2–5% in Caucasians, 18–23% in Asians, > 87% PM in Caucasians is *2 and *3; > 99% PM in Asians has *2 and *3. CYP2C19*2 homozygotes did not respond to antiangiogenic drug thalidomide treatmentNo

rs4986893*3, 17948G>A, exon 4 premature stopYes

rs28399504*4, transcription ablationFailed

90033C>T, R433W, *5A, *5BNo enzymatic activityYes

*7, 19294T>ASplicing defect, no enzymatic activityYes

CYP2D6rs16947*2, 2851C>T, R296CNormal, nucleotide position corrected according to [47]Yes

rs3892097 or rs1800716*4, 1847G>A, splicing defectThe CYP2D6 PM is about 5–10% of Caucasians. 99% PM has *3, *4, *5, *6, *7, *8 and *11. *3, *5 and *6 are deletionsYes

rs28371704983A>G, H94RIn *4A, *4B, *4F, *4G, *4H and *4JFailed

rs5030867*7, 2936A>C, H324PNo enzymatic activityYes

rs5030865*8, 1759G>TStop codon, no enzymatic activityYes

rs1065852*10, 100C>T, P34SDecrease enzymatic activityYes

rs5030863*11, 882G>CSplicing defect, no enzymatic activityYes

rs28371706*17, 1022C>T, T107IDecrease enzymatic activityYes

rs28371717*33, 2484G>T, A237SNormalYes

*44, 2951G>CSplicing defect, no enzymatic activityYes

CYP3A4rs11773597*1F, m747C>GTrans-regulation of gene expression is important. Overall, no major pharmacokinetic consequences for the identified CYP3A4 SNPs have been observed for the metabolism of anti-cancer drugs [12]Yes

rs2740574*1B, m392A>GYes

*4, 13989A>G,In AF209389Yes

*8, 14026G>AIn AF209389, R130QYes

CYP3A5rs28365083*2, 27289C>A, T398NFailed

rs776746*3, 6986A>G, splicing inclusion*3 is the most frequent polymorphism (about 90% in Caucasians). Splicing defect, severely decrease of enzymatic activity [12]Yes

rs28365085*3d, 31551T>C, I488TYes

*5, 12952T>CSplicing defectYes

*8, 3699C>T, R28CDecreased enzymatic activityYes

rs28383479*9, 19386G>A, A337TDecreased enzymatic activityFailed

rs15524*10, 31611C>TDecreasde enzymatic activityYes

DPYDrs3918290splice variant IVS14+1G>A*2A, Skipping exon 14, ↑ 5FU neurotoxicity [12]Yes

NQO1rs1800566*2, C609T, R187S*2 and *3 have reduced protein level and enzymatic activity. NQO1 is needed for the activation of mitomycin C, 17AAG (HSP90 inhibitor) and inactivation of benzene-like leukemogenic agents [13]Yes

rs4986998*3, C465T, R139WYes

Phase II metabolism enzymes
NAT allele nomenclature [26]:
UGT allele nomenclature [25]:


NAT2rs1801280341T>C, I114T, *5A to*5J, *14C and *14FAlleles with decreased activity include NAT2*5B, NAT2*6A, NAT*7A or B, NAT2*10, NAT2*14A or B, NAT2*17, NAT2*18 and NAT2*19 [12, 14]
Low NAT2 activity is related to the increased risk of isoniazid hepatotoxicity

rs1799929481C>T, L161L, *5A, *5B, *5F, *5G, *5H, *5I, *6E, *11A, *11B, *12C and *14CYes

rs1208803A>G, K268R,*5B, *5C, *5F, *5G, *5H, *5I, *6C, *12A, *12B, *12C, *12D, *14E and *14FYes

rs1041983282C>T, Y94Y, *13, *5G, *5J, *6A, *6C, *6D, *7B, *12B, *14B, *14D, *14GYes

rs1799930590G>A, R197Q *5E, *5J, *6A, *6B to *6E, *14DYes

rs1799931, 857G>A, G286E *7A, *7BYes

499G>A in sequence X14672, E167K, *10Yes

rs1801279191G>A, R64Q *14A to *14G,Yes

434A>C A in sequence X14672, Q145P, *17Yes

845A>C A in sequence X14672, K282T, *18Yes

rs1805158190C>T, R64W, *19Yes

TPMTrs1800462*2, 238G>CNull genotype associated with hematopoietic thiopurine toxicity, homozygous frequency 1/300 [4]No

rs1800460*3A, 460G>ANo

rs1142345*3C, 719A>GNo

UGT1A1TA (5–8) TAAUGT1A1 *28 (7 TAs) associated with increased irinotecan toxicity. Caucasians ~32%No

rs4148323211G>A, G71R, *6Reduced enzymatic activityYes

rs349937801456T>G, Y486D, *7Yes

rs35350960686C>A, P229Q, *27Yes

247T>C, F83L, *62Causing Gilbert's syndromeYes

GSTT1Deletion causing null genotypeNull allele has been associated with better or poorer survival in leukemia patients following chemotherapy [12]No

GSTP1rs947894313A>G I105VVal associated with decreased enzyme activity and increased survival after 5FU/oxaliplatin treatment of colorectal cancer patients [54]Yes

GSTM1Deletion causing null genotypeNull allele is associated with increased survival after chemotherapy for multiple cancers [13, 14]No

SULT1A1rs9282861*2, R213H, HaeIIHis/His has lower enzymatic activity and is associated with poor survival following tamoxifen therapy [55]No

Transporter Genes


ABCB1rs10456423435C>TC3435 associated with higher drug transport activityYes



ABCC2rs22736971249G>A, Val417Ile1249AA associated with decreased mRNA [56]Yes

ABCG2rs2231142421C>A, Q141KMinor alleles with lower BRCP expression, enhanced drug sensitivity [12]Yes

rs2231137G34 G>A V12MNo

944–949 deletionNo

SLC19A1rs105126680G>A Arg27HisPatients with the 80AA genotype had higher plasma MTX levels, suggesting decreased cellular uptake of MTXYes

SLCO1B1/SCL21A6rs4149056T521C, Val174Ala, *5*5 and *15 are associated with decreased transport activity [57]Yes

rs2306283Asp130Asn, *15Yes

DNA repair genes


BRCA2rs144848N372HCancer risk [51]Yes

OGG1rs1052133S326CCancer risk [51]Yes

XRCC1rs1799782R194WCancer risk [51]Yes

rs25487R399QGln399 associated with oxaliplatin/5-FU resistanceYes


ERCC2/XPDrs13181K751QLys751 associated with improved oxaliplatin/5-FU treatment outcome [52]Yes

TP53rs1042522R72PCancer riskFailed

MGMTrs12917262C>T, L84FDecreased repair of DNA damage [58]Yes

CHEK21100delCProtein truncation, cancer risk [59]No

Drug target, pathway genes


DHFRrs5030762829T>CSNP 829T>C located in the untranslated region of the DHFR, associated with ↑ of DHFR mRNA, ↓ responsiveness to methotrexateNo

MTHFRrs1801133677C>T, A222Vminor allele frequency 24–46%% in Caucasians, T allele is associated with reduced enzyme activity, increased toxicity to methotrexate [13, 53]Yes
rs18011311298A>C, E429AReduced MTHFR enzyme activity [13, 53]Yes

TYMS2–9 28 bp repeats in the 5' promoter enhancer3 repeats ↑ RNA, TSER*3 associated with drug resistance of 5FU and methotrexateNo

CDArs207267179A>C, K27QMinor allele has lower activity to inactivate gemcitabine than the wild-type [60]Yes

208G>A, A70T70TT has lower activity to inactive cytidine and ara-C than the wild-type [61]Yes

Cell cycle genes

CCND1rs603965870A>GAlternative transcript encodes a protein with enhanced cell transformation activity, and modifies caner risk [62]Yes