Genetic variations and haplotypes of ABCC2 encoding MRP2 in a Japanese population.
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.
Sai
Kimie
K
Project Team for Pharmacogenetics, National Institute of Health Sciences, Tokyo, Japan. sai@nihs.go.jp
Saito
Yoshiro
Y
Itoda
Masaya
M
Fukushima-Uesaka
Hiromi
H
Nishimaki-Mogami
Tomoko
T
Ozawa
Shogo
S
Maekawa
Keiko
K
Kurose
Kouichi
K
Kaniwa
Nahoko
N
Kawamoto
Manabu
M
Kamatani
Naoyuki
N
Shirao
Kuniaki
K
Hamaguchi
Tetsuya
T
Yamamoto
Noboru
N
Kunitoh
Hideo
H
Ohe
Yuichiro
Y
Yamada
Yasuhide
Y
Tamura
Tomohide
T
Yoshida
Teruhiko
T
Minami
Hironobu
H
Matsumura
Yasuhiro
Y
Ohtsu
Atsushi
A
Saijo
Nagahiro
N
Sawada
Jun-ichi
J
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
D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human