title: Genetic variations and haplotypes of ABCC2 encoding MRP2 in a Japanese population.
abstract: The multidrug resistance-associated protein 2 (MRP2) encoded by the ABCC2 gene is expressed in the liver, intestine and kidneys and preferentially exports organic anions or conjugates with glucuronide or glutathione. In this study, all 32 exons and the 5'-flanking region of ABCC2 in 236 Japanese were resequenced, and 61 genetic variations including 5 novel nonsynonymous ones were detected. A total of 64 haplotypes were determined/inferred and classified into five *1 haplotype groups (*1A, *1B, *1C, *1G, and *1H) without nonsynonymous substitutions and *2 to *9 groups with nonsynonymous variations. Frequencies of the major 4 haplotype groups *1A (-1774delG), *1B (no common SNP), *1C (-24C>T and 3972C>T), and *2 [1249G>A (Val417Ile)] were 0.331, 0.292, 0.172, and 0.093, respectively. This study revealed that haplotype *1A, which has lowered activity, is quite common in Japanese, and that the frequency of *1C, another functional haplotype, was comparable to frequencies in Asians and Caucasians. In contrast, the haplotypes harboring 3972C>T but not -24C>T (*1G group), which are reportedly common in Caucasians, were minor in Japanese. Moreover, the allele 1446C>T (Thr482Thr), which has increased activity, was not detected in our Japanese population. These findings imply possible differences in MRP2-mediated drug responses between Asians and Caucasians.
authors.affiliation: Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan. sai@nihs.go.jp
authors.forename: Kimie
authors.initials: K
authors.lastname: Sai
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Masaya
authors.initials: M
authors.lastname: Itoda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Fukushima-Uesaka
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nishimaki-Mogami
authors.forename: Shogo
authors.initials: S
authors.lastname: Ozawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Maekawa
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Nahoko
authors.initials: N
authors.lastname: Kaniwa
authors.forename: Manabu
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Shirao
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hideo
authors.initials: H
authors.lastname: Kunitoh
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ohe
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hironobu
authors.initials: H
authors.lastname: Minami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Saijo
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Sawada
mesh_terms: D044466:Asian People; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People
chemical_list: D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human