Genetic polymorphisms of copper- and platinum drug-efflux transporters ATP7A and ATP7B in Japanese cancer patients.
ATP7A and ATP7B are involved in cellular resistance to platinum compounds such as cisplatin. By sequencing ATP7A, 38 genetic variations, including 30 novel ones were detected from 203 Japanese cancer patients. Of these, seven nonsynonymous variations were found: novel 1030A>G (R344G), 2111A>G (Q704R), 2200C>A (Q734K), 2948C>T (T983M) and 3112G>A (V1038I) at 0.004 frequencies and known 2299G>C (V767L) and 4390A>G (I1464V) at 0.351 and 0.075 frequencies, respectively. Regarding ATP7B, 28 novel and 33 known genetic variations were detected including 13 nonsynonymous ones: novel 1258A>G (M420V), 1426G>A (A476T), and 2401A>C (T801P) were found at 0.002, 0.005, and 0.002, respectively and known 1216G>T (A406S), 1366G>C (V456L), 2495A>G (K832R), 2785A>G (I929V), 2855G>A (R952K), 2871delC (P957PfsX9), 3419T>C (V1140A), 3836A>G (D1279G), 3886G>A (D1296N) and 3889G>A (V1297I) at 0.483, 0.463, 0.387, 0.005, 0.384, 0.005, 0.387, 0.002, 0.012, and 0.015 frequencies, respectively. Linkage disequilibrium between detected variations was also analyzed. Our results would provide fundamental and useful information for genotyping ATP7A and ATP7B in the Japanese and probably other Asian populations.
Fukushima-Uesaka
Hiromi
H
Project team for Pharmacogenetics, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Saito
Yoshiro
Y
Maekawa
Keiko
K
Kurose
Kouichi
K
Sugiyama
Emiko
E
Katori
Noriko
N
Kaniwa
Nahoko
N
Hasegawa
Ryuichi
R
Hamaguchi
Tetsuya
T
Eguchi-Nakajima
Takako
T
Kato
Ken
K
Yamada
Yasuhide
Y
Shimada
Yasuhiro
Y
Yoshida
Teruhiko
T
Yamamoto
Noboru
N
Nokihara
Hiroshi
H
Kunitoh
Hideo
H
Ohe
Yuichiro
Y
Tamura
Tomohide
T
Ura
Takashi
T
Saito
Miyuki
M
Muro
Kei
K
Doi
Toshihiko
T
Fuse
Nozomu
N
Yoshino
Takayuki
T
Ohtsu
Atsushi
A
Saijo
Nagahiro
N
Matsumura
Yasuhiro
Y
Okuda
Haruhiro
H
Sawada
Jun-ichi
J
D020121:5' Untranslated Regions / Q000235:genetics; D000251:Adenosine Triphosphatases / Q000235:genetics*; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics*; D002945:Cisplatin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D033721:Equilibrative Nucleoside Transporter 1; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D004930:Inuit / Q000235:genetics; D015810:Linkage Disequilibrium; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010984:Platinum / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics
D020121:5' Untranslated Regions; D027682:Cation Transport Proteins; D033721:Equilibrative Nucleoside Transporter 1; D026901:Membrane Transport Proteins; D010984:Platinum; D003300:Copper; D014453:Glucuronosyltransferase; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases; D002945:Cisplatin