Project team for Pharmacogenetics, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Drug Metab Pharmacokinet. 2009;24(6):565-74. doi: 10.2133/dmpk.24.565.
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.
ATP7A 和 ATP7B 参与细胞对顺铂等铂类化合物的耐药性。通过对 ATP7A 的测序，从 203 名日本癌症患者中检测到 38 种遗传变异，包括 30 种新的变异。其中，发现 7 种非同义变异：新的 1030A>G（R344G）、2111A>G（Q704R）、2200C>A（Q734K）、2948C>T（T983M）和 3112G>A（V1038I），频率分别为 0.004、0.004、0.004、0.004 和 0.004，已知的 2299G>C（V767L）和 4390A>G（I1464V）的频率分别为 0.351 和 0.075。关于 ATP7B，检测到 28 种新的和 33 种已知的遗传变异，包括 13 种非同义变异：新的 1258A>G（M420V）、1426G>A（A476T）和 2401A>C（T801P）的频率分别为 0.002、0.005 和 0.002，已知的 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）和 3889G>A（V1297I）的频率分别为 0.483、0.463、0.387、0.005、0.384、0.005、0.387、0.002、0.012 和 0.015。还分析了检测到的变异之间的连锁不平衡。我们的结果将为日本人群（可能还有其他亚洲人群）中 ATP7A 和 ATP7B 的基因分型提供基础和有用的信息。
