Impact of membrane drug transporters to resistance of small molecule tyrosine kinase inhibitors

Claudia Neul, Elke Schaeffeler, Alex Sparreboom, Stefan Laufer, Matthias Schwab, Anne T. Nies

Supplementary Table 1. Genetic variants tested in pharmacogenetic association studies

Transporter / Genetic variant a common name / Genetic variant a
dbSNP ID / Location b / Consequence type b / Allele frequency (%) in population b
Allele / European / African / American / East Asian / South Asian
ABCB1 / 1236C>T / rs1128503 / Exon / Synonymous variant (Gly412) / T / 42 / 14 / 40 / 63 / 59
2677G>T/A / rs2032582 / Exon / Missense variant
(Ala893Ser/Thr) / A
T / 41
2 / 2
<1 / 37
6 / 40
13 / 59
5
3435C>T / rs1045642 / Exon / Synonymous variant (Ile1145) / T / 52 / 15 / 43 / 40 / 57
ABCC2 / -24C>T / rs717620 / 5’ UTR / Regulatory region variant / T / 21 / 3 / 17 / 22 / 10
1249G>A / rs2273697 / Exon / Missense variant
(Val417Ile) / T / 20 / 19 / 16 / 10 / 28
3972C>T / rs3740066 / Exon / Synonymous variant (Ile1324) / T / 37 / 22 / 34 / 25 / 30
ABCG2 / -15622C>T / rs55930652 / Intron / T / 31 / 3 / 21 / 21 / 11
34G>A / rs2231137 / Exon / Missense variant
(Val12Met) / T / 6 / 6 / 24 / 33 / 15
421C>A / rs2231142 / Exon / Missense variant
(Gln141Lys) / A / 9 / 1 / 14 / 29 / 10
1143C>T / rs2622604 / Intron / T / 24 / 11 / 20 / 20 / 12
SLC22A1/
OCT1 / -1795G>A / rs6935207 / Upstream gene variant / A / 19 / 43 / 31 / 52 / 28
156T>C / rs1867351 / Exon / Synonymous variant (Ser52) / C / 18 / 33 / 29 / 39 / 20
181C>T / rs12208357 / Exon / Missense variant
(Arg61Cys) / T / 6 / <1 / 2 / 0 / 2
262T>C / rs55918055 / Exon / Missense variant
(Cys88Arg) / C / <1 / 0 / 0 / 0 / 0
480GC / rs683369 / Exon / Missense variant
(Leu160Phe) / G / 21 / 1 / 11 / 15 / 17
659G>T / rs36103319 / Exon / Missense variant
(Gly220Val) / T / 0 / <1 / 0 / 0 / 0
848C>T / rs4646277 / Exon / Missense variant
(Pro283Leu) / T / 0 / 0 / 0 / <1 / 0
859C>G/T / rs4646278 / Exon / Missense variant
(Arg287Gly) / T / <1 / 0 / 0 / 0 / 1
1022C>T / rs2282143 / Exon / Missense variant
(Pro341Leu) / T / 1 / 8 / 2 / 13 / 8
1201G>A / rs34130495 / Exon / Missense variant
(Gly401Ser) / A / 2 / <1 / 1 / 0 / <1
1222A>G / rs628031 / Exon / Missense variant
(Met408Val) / A / 41 / 27 / 22 / 26 / 39
1239G>A / rs34888879 / Exon / Synonymous variant (Ala413) / A / 0 / 1 / <1 / 0 / 0
1258_1260delATG / rs202220802 / Exon / Missense variant
(Met420del) / del / 18 / 5 / 29 / 0 / 15
1275_1276
+6delTGGTAAGT / rs113569197 / Splice donor variant / insert / 42 / 26 / 22 / 26 / 39
1386-2964C>A / rs622342 / Intron / C / 38 / 18 / 40 / 15 / 25
1393G>A / rs34059508 / Exon / Missense variant
(Gly465Arg) / A / 2 / 0 / 2 / 0 / 0
1503G>A / rs41267797 / Exon / Synonymous variant (Val501) / A / 2 / 20 / 4 / 0 / 1
SLC22A4/
OCTN1 / 1507C>T / rs1050152 / Exon / Missense variant
(Leu503Phe) / T / 39 / 2 / 24 / <1 / 9
SLC22A5/
OCTN2 / -207C>G / rs2631367 / 5’ UTR / Regulatory region variant / C / 44 / 42 / 33 / <1 / 10
-2087G>C / rs2631372 / Intron / C / 32 / 18 / 26 / 35 / 60
SLCO1A2/
OATP1A2 / -361G>A / rs3764043 / Intron / A / 2 / <1 / 9 / 17 / 18
38T>C / rs10841795 / Exon / Missense variant
(Ile13Thr) / C / 13 / <1 / 7 / <1 / 7
516A>C / rs11568563 / Exon / Missense variant
(Glu172Asp) / C / 7 / 1 / 4 / 0 / 2
SLCO1B3/
OATP1B3 / 334T>G / rs4149117 / Exon / Missense variant
(Ser112Ala) / T / 14 / 64 / 16 / 30 / 9

aData retrieved from http://www.ncbi.nlm.nih.gov/projects/SNP/ bData retrieved from http://www.ensembl.org

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