title: Genetic polymorphisms of copper- and platinum drug-efflux transporters ATP7A and ATP7B in Japanese cancer patients.
abstract: 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.
authors.affiliation: Project team for Pharmacogenetics, National Institute of Health Sciences, Tokyo 158-8501, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fukushima-Uesaka
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Emiko
authors.initials: E
authors.lastname: Sugiyama
authors.forename: Noriko
authors.initials: N
authors.lastname: Katori
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Takako
authors.initials: T
authors.lastname: Eguchi-Nakajima
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Ura
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Kei
authors.initials: K
authors.lastname: Muro
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fuse
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Haruhiro
authors.initials: H
authors.lastname: Okuda
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: 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
chemical_list: 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