ﾁ ｨｨ05ｨｹｨｪ ｨｨ07ｨｪｨｨ02 ｨｪｨ ｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ ｨｨ 05ｨｺ ｨｨ ｨｬ02ｨｦ 09ｨｰ 09ｨ ｨｬ02ｨｪ ｨｰ06

Transcription

1 130005ｨｨ07ｨｪｨｨ ｨｪ02ｨｰｨｨ ﾂ0209ｨｺｨｨ01 00ｨ ｨｺｨｰ ﾂ ｨｺｨ ｨｪｨ ｨｺ06ｨ ｨｺｨｰｨｨ09ｨｪｨｮ06 ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪｨｮ06 ｨｰ0208ｨ 07ｨｨ06 ( )* 06ｨｮ ｨｬｨ ｨｪ ｨｨ08ｨｮ ｨｨｨｨ ｨｨｨｬ ｨ ｨｪ060909ｨｺ , , ｨｺ 09ｨ, ｨｮ05. 01ｨ ｨｬｨ 0502ｨｨ,16, ｨｰ0205./00ｨ ｨｺ09: , e-ma il: de il.ru 0604ｨｮ ﾂ02ｨｪｨｨ ｨｪ02ｨｰｨｨ ﾂ0209ｨｺｨｨ01 00ｨ ｨｺｨｰ ﾂ ｨｺｨ, ｨ ｨｨｨｨ080609ｨ ｨｪｨｪ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ ﾂ02ｨｪｨｨ ﾁ-ｨｨｨｪ0002ｨｺ02ｨｨｨｨ, ｨｰ ｨ 03 - ｨｪ04ｨｬ ｨｪｨ 0708ｨ ｨｪｨｨ02ｨｬ 09 ｨ 0608ｨｹｨ ｨｪ0206 ｨｨ ｨｬ. 05ｨ ｨｪｨｨ ｨ ｨｰｨｨ0502ｨｰｨｨ07 ｨ ｨ ｨｪｨ 08ｨｮ0302ｨｪ06 ｨｬｨｪ ｨ ｨｨｨ 02ｨｨｨｦ ｨｬ020301ｨｮ 08ｨ 0405ｨｨ ﾂｨｪ04ｨｬｨｨ ｨ ｨｹｨｪ04ｨｬｨｨ 09ｨ 08ｨｨｨ ｨｪｨｰｨ ｨｬｨｨ 0002ｨｪ0609 ﾂ ｨｺｨ ｨｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ06 ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪ06ｨｦ ｨｰ0208ｨ 07ｨｨｨｨ (080406) 0006 ﾁ-ｨｨｨｪ0002ｨｺ02ｨｨｨｨ ｨ 02ｨｪｨｪ04ｨｦ ｨｨｨｪｨｰ ｨｨ ｨ ｨｰ020502ｨｦ ｨｰｨ ｨｰ ｨ ｨｹｨｪ ｨ 08ｨｨｨ ｨｪｨｰ ｨｪ0609, ｨ ｨｨｨｨ080609ｨ ｨｪｨｪ ｨｰ ｨｬｨｨ ｨｪ02ｨｪｨｨ07ｨｬｨｨ, ｨｪｨｨｨｺｨ 06ｨｴｨｨｨｬｨｨ 0708ｨｨ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨｨｨ ｨｪ0600ｨｨ02 ｨｨ04 ｨｨ04ｨｮ ﾂ02ｨｪｨｪ0401 ｨ ｨｨｨ 02ｨｨｨｦ ｨｰ0802ｨ ｨｮ06ｨｰ ｨｪｨｨ ｨｰ ｨ 06ｨｴｨｨ01 ｨｨ ｨｮｨｰ06 ﾂ - ｨｪ0706ｨｴｨｨ01 ｨｨ ｨ ｨｪｨｨｨｦ ｨ ｨｪｨｪ06ｨｦ 09ｨｰｨ ｨｰｨｹ ｨｪ 06ｨ ｨｪ02ｨｰｨｨ ﾂ0209ｨｺｨｨ01 00ｨ ｨｺｨｰ , 01ｨ 06ｨｴｨｨｨｦ ｨｺ0506 ﾂ ｨｺ 0706ｨｪｨｨｨｬｨ ｨｪｨｨ ｨｬ0603ｨｪ0609ｨｰｨｨ ｨｪｨｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｨ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨ ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨ 02ｨｨ02ｨｪｨｰ ﾂ ｨ : 0006 ﾁ-ｨｨｨｪ0002ｨｺ02ｨｨ07, 0002ｨｪ02ｨｰｨｨ ﾂ0209ｨｺｨｨ02 00ｨ ｨｺｨｰ ｨｨｨｪｨ, ｨｺ06ｨ ｨｺｨｰｨｨ09ｨｪｨ 07 ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪｨ 07 ｨｰ0208ｨ 07ｨｨ ｨｪｨｨ02 00ｨｪ ｨｪｨｪｨ ｨｬ02 01ｨｨ 02ｨｨｨｪ 09ｨｺｨｮ ｨ ｨｺ ｨｰｨｨ ｨｺｨｮ 06ｨｺ ｨｰ ｨｪｨ 04ｨ ｨｪｨ ｨｰｨ 07ｨ 01 06ｨｺｨ 04ｨ 05ｨ 09ｨｹ ｨｪ ｨｰｨ ｨｰ06 ﾂ ｨｪ ｨｺ ｨｰｨｨ09 ｨｪ04ｨｬ ｨｨｨｪ 09ｨｰ 08ｨｮ ｨｬ02ｨｪ ｨｰ06ｨｬ 09 ｨ 06 08ｨｹ ｨ ﾁ-ｨｨｨｪ 0002ｨｺ 02ｨｨ02ｨｦ ｨｨ ｨｬ, 0601 ｨｪｨ ｨｺ ｨｮ 06 ｨｴ ｨｪｨｨ ｨｺ06 ｨ ｨｺ - ｨｰｨｨ09ｨｪ06ｨｦ ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪ06ｨｦ ｨｰ0208ｨ 07ｨｨｨｨ ( ) ｨｨ ｨｮ ｨｴ02 09ｨｰ 0902ｨｪ ｨｪ ｨｨｨｰｨｹ 0102ｨｦ 09ｨｰ 0902ｨｪ ｨｪ0609ｨｰｨｹ 0502 ﾂ02 ｨｪｨｨ ﾁ-ｨｨｨｪ - 00ｨｨ 02ｨｨ ｨ ｨｪ ｨｪ ｨｨ02, ｨｮ ｨｨ ﾂｨｨｨｰｨｹ ｨｨ ｨｰ02 05ｨｹ ｨｪ0609ｨｰｨｹ ｨｨ ｨｨｨｰｨｹ ｨｺｨ ﾂ0209ｨｰ0906 ｨｨ01 03ｨｨ04ｨｪｨｨ ｨｹ040609ｨ ｨｪｨｨ ｨｨ ｨｺ ｨｮ090205ｨｨ ﾂ02ｨｪｨｨ06 ﾂｨｨ0905ｨ ｨｪｨ ｨｮ ﾂｨｪ0401 ｨｨ ｨ ｨｪｨｨｨｦ ｨｪｨｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｨ ｨｨｨｬ02ｨｪ02ｨｪｨｨ07, ﾂｨｰ06, ﾂ ｨｹ, ｨｨ ｨ ｨｪｨ 08ｨｮ03ｨｨｨｰｨｹ 0601ｨｨｨｪ ｨｨ04 09ｨ 03ｨｪ02ｨｦ03ｨｨ01 00ｨ ｨｺｨｰ , 06ｨｺｨ ｨ 06ｨｴｨｨ ｨｨ07ｨｪｨｨ02 ｨｪｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨ ｨ 0608ｨｹｨ ﾁ-ｨｨｨｪ0002ｨｺ02ｨｨ02ｨｦ ｨｨ ｨｬ, ｪ 0002ｨｪ06ｨｬ ﾂ ｨｺｨ. 0306ｨｨ09ｨｺ ｨ ｨｹｨｪ ｨ 08ｨｨｨ ｨｪｨｰ ｨｪ0609 ﾂ ｨｺｨ, ｨ ｨｨｨｨ080609ｨ ｨｪｨｪ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ , ｨｰ0907 ｨｪｨ 01ｨ ｨｪｨｪ04ｨｦ ｨｬ06ｨｬ02ｨｪｨｰ ｨｬ02ｨｪｨｨ 0601ｨｪｨｨｨｬ ｨｨ04 09ｨ 03ｨｪ02ｨｦ03ｨｨ01 ｨｪｨ 0708ｨ ｨｪｨｨｨｦ ｨｪｨ ｨｮ ﾂｨｪ0401 ｨｨ040409ｨｺｨ ｨｪｨｨｨｦ ｨ 0608ｨｹｨ ﾁ-ｨｨｨｪ 0002ｨｺ 02ｨｨ02ｨｦ ｨｨ ｨｬ ｨ ｨｪ ｨｪ06ｨｦ 09ｨｰｨ ｨｰｨｹ02 05ｨｰ06 ｨｨ ｨｪｨ ｨｰ08ｨ 0302ｨｪｨｨ ｨｨ0102 ｨｪ02ｨ 0605ｨｹ ｨ ｨ ｨｪ02ｨｰｨｨ ﾂ0209ｨｺｨｨｨｬ 00ｨ ｨｺｨｰ0608ｨ ｨｬ ﾂ ｨｺｨ, ｨ ｨｨｨｨ080609ｨ ｨｪｨｪ04ｨｬ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪ ｨ 08ｨ ｨｰ ｨｺｨ ｨｬ ｨｬ 09 ｨｬｨｨ ｨｨｨｰ ｨ 0605ｨｹ0302 ｨｨ ｨ ｨｪｨｨｨｦ, ｨｴ00ｨｪｨｪ ｨｨ07ｨｪｨｨ ｨ 02ｨｪｨｪ0609ｨｰ02ｨｦ 0002ｨｪ06 - ｨｬｨ ﾂ ｨｺｨ ｨｪｨ ｨｮ ｨｪ0609ｨｰｨｹ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨ ｨ 02ｨｪ - ｨｪ04ｨｦ ｨｨｨｪ ｨｰ ｨｨ ｨ ｨｰ ｨｦ ｨｰｨ ｨｰ 0905ｨｨ 07 ｨｪｨｨ ｨｪ02 ｨｰｨｨ ﾂ02 09ｨｺｨｨ01 00ｨ ｨｺ ｨｰ ﾂ ｨｺｨ ｨｪｨ ｨｺ ｨｰｨｨ09 ｨｪ0609ｨｰｨｹ 0708ｨｨ - ｨｬ02 ｨｪ02 ｨｪｨｨ07 08ｨ 04 ｨｪ ｨｮ0707 ｨ ｨｪ ｨｰｨｨ 0802ｨｰ ｨｨ 08ｨｮ09 ｨｪ ｨ 08ｨ ｨｰ0609 ｨｨ ｨｪｨｨｨｺｨｪ060902ｨｪｨｨ ｨｨ 05ｨｰ06ｨｬ 08ｨ 04ｨｪ0606ｨ 08ｨ 04ｨｪ ｨｪ02ｨｪｨｨｨｦ ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨ 02ｨｨ02ｨｪｨｰ ｨｰｨ ｨｺｨｨｨｬ 0002 ｨｪ02 ｨｰｨｨ ﾂ02 09ｨｺｨｨｨｬ 00ｨ ｨｺ ｨｰ0608ｨ ｨｬ 06ｨｰｨｪ ｨｰ 0907 ｨｬ02 ｨｰｨ ｨ 06-05ｨｨ ﾂ02 09ｨｺｨｨ ｨｬ02ｨｪ ｨｰ ｨｺｨｨｨｬ 06ｨ 08ｨ ｨｬ 0905ｨｮ03ｨｨｨｰ ｨ 06 05ｨｹ - 03ｨ ｨｮ07 07ｨ ｨｬ02ｨｪ ｨｰ ｨｮ ｨｬ02ｨｦ 09ｨｰ 09ｨ 02ｨｨ ｨｰ ｨｬ0609 P450 (cytochrome P450, CYP450), 0609ｨｪ0609ｨｪ06ｨｦ 00ｨｮｨｪｨｺ02ｨｨ02ｨｦ ｨｺ06ｨｰ ｨｰ0907 ｨｺｨ ｨｰｨ 05ｨｨ04 06ｨｺｨｨ090502ｨｪｨｨ ｨ ｨｪｨｨ ﾂ0209ｨｺｨｨ01 09ｨｮｨ 09ｨｰｨ ｨｪ02ｨｨｨｦ ｨｹ 03ｨ 07 ﾂｨ 09ｨｰｨｹ 0902 ｨｬ02ｨｦ 09ｨｰ 09ｨ CYP ﾂ02ｨｪｨ 09 ｨｬ02 ｨｰｨ - ｨ 06 05ｨｨ04ｨｬ ｨｨ ｨ ｨｨ06 ｨ ｨｺ ｨｰｨｨ 09ｨ 02ｨｨ ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ0609, ｨｮ ﾂｨ 09ｨｰ 09ｨｮ % 06ｨ ｨｴ ﾂｨｨ09 05ｨ 08ｨ 04 05ｨｨ ﾂ ｨｪ0401 ｨｬ02 ｨｰｨ ｨ 06 05ｨｨ ﾂ02 09ｨｺｨｨ ｨ ｨｺ 02ｨｨｨｦ, 0708ｨｨ 05ｨｰ06ｨｬ, ｨｺｨ ｨｺ 0708ｨ 09ｨｨ 0506, ﾂ02ｨｬ 09ｨｨ 05ｨｹ ｨｪ ｨｺ ｨｨ07 01ｨ ｨｪ ｨｪ ｨｬ02ｨｪ ｨｰ0609, ｨｰ02ｨｬ ｨｪｨｨ 0302 ｨｺ06ｨｪ 0202ｨｪ ｨｰ 08ｨ 02ｨｨ ｨｺｨ 08-09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ ｨｺ0502ｨｰ ｨｺ02, ｨｨ ｨｪｨ 06 ｨ ｨｰ. 0308ｨｨ ｨｬ02 ｨｪｨｨ ｨｰ02 05ｨｹ ｨｪ06 ｨｺ ｨ ｨｲ 02ｨｺ ｨｰ06ｨｬ 0905ｨｨ 07 ｨｪｨｨ07 01ｨ ｨｪ ｨｪ06ｨｦ 0008ｨｮ ｨｰ ｨ ｨｪｨｨ ｨ 08ｨ ｨｰ ｨｺ0502ｨｰ ｨｺｨ 01, ｨｮ02ｨｨ08ｨｮ06ｨｴｨｨ ﾁ ｨ 02ｨｨ02ｨｪｨｰ0609, ｨｨｨｬ0206ｨｴｨｨ01 ｨｪｨｨ04ｨｺｨｮ06 05ｨｺ ｨｨ06 ｨｨ05ｨｨ ｨｪ ｨｰｨ ｨｰ06ｨｺ ﾂｨ 09ｨｰｨｨ ｨｬ02ｨｰｨ ｨ 0605ｨｨ ﾂ0209ｨｺｨｨ ｨｬ02ｨｪ ｨｰ0609, ｨｪｨ ｨ ｨ 02ｨｰ ｨｺｨ ｨ 04 ｨｬｨ ｨｰｨｨ ﾂ02 09ｨｺｨ 07 ｨｺ06ｨｪ 0202ｨｪ ｨｰ - 08ｨ 02ｨｨ ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ0609, ｨｺ06 ｨｰ06 08ｨ 07, ﾂ ｨｹ, ｨｬ ｨｰ ｨ ｨｰｨｹ ｨｰ06ｨｺ09ｨｨ ﾂ ｨｪ0609ｨｰｨｹ. 01ｨ ｨｰｨｨ09, 0708ｨｨ 0905ｨｨ03 - ｨｺ06ｨｬ ｨｺ06ｨｦ ｨ ｨｺ ｨｰｨｨ09 ｨｪ06 09ｨｰｨｨ ｨｬ02ｨｪ ｨｰ ｨｮ CYP450 ｨｺ06ｨｪ 0202ｨｪ ｨｰ 08ｨ 02ｨｨ ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ0609 ｨｪ ｨｰｨｨ 00ｨ 02ｨｰ ｨｮ080609ｨｪ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｨ, ｨｰｨ ｨｰ06 ﾂｨｪ06ｨｦ ｨｨｨｪ00ｨｨｨ ｨｨ080609ｨ - ｨｪｨｨ07 09ｨｨ08ｨｮ09ｨ. 06ｨ ｨｺ, ｨｮ09ｨｰｨ ｨｪ ｨｪ06, ﾂｨｰ06 ｨｨ ｨｬ02ｨｪｨｰ CYP2D6 ｨｬ02 ｨｰｨ ｨ 06-05ｨｨ 04ｨｨ 08ｨｮ 02ｨｰ ｨ 06 05ｨｹ 03ｨｮ06 ﾂｨ 09ｨｰｨｹ ｨ ｨｪ ｨｰｨｨ 0802ｨｰ ｨｨ 08ｨｮ09 ｨｪ ｨ 08ｨ - ｨｰ ｨｹ ｨｪ ｨ 08ｨｨ ｨ ｨｪ ｨｰ04 CYP2D6*9, CYP2D6*10 ｨｨ CYP2D6*17 ｨ ｨｨｨｨ080609ｨ ｨｪ04 09 ｨｨｨｪ00ｨｨｨ ｨｨ080609ｨ ｨｪｨｨ02ｨｬ ｨｨ ｨｬ02ｨｪ ｨｰｨ CYP2D6, 09 ｨｰ ｨｬ07 ｨｺｨ ｨｺ 0708ｨｨ 09ｨｮｨｰ 09ｨｰ 09ｨｨ02 ｨ CYP2D6*2 ｨｮ09ｨｨ 05ｨｨ 09ｨ 02ｨｰ ｨｬ02ｨｪ ｨｰｨ ｨｰｨｨ09 ｨｪｨｮ06 ｨ ｨｺ ｨｰｨｨ09 ｨｪ0609ｨｰｨｹ ｨｹ ｨｪ ｨ 08ｨｨ ｨ ｨｪ ｨｰ04 ｨｨ ｨｬ02ｨｪ ｨｰ0609 CYP2C9 ｨｨ CYP2C19 ｨｰｨ ｨｺ ｨ 06ｨｰ 09 ｨｨｨｪｨ ｨｺ ｨｰｨｨ 09ｨ 02ｨｨ02ｨｦ 01ｨ ｨｪ ｨｪ0401 ｨｨ ｨｬ02ｨｪ ｨｰ0609 ｨｨ05ｨｨ 09ｨｪｨｨ0302ｨｪｨｨ02ｨｬ ｨｨ01 ｨ 0000ｨｨｨｪｨｪ0609ｨｰｨｨ ｨｺ 09ｨｮｨ 09ｨｰ08ｨ ｨｰｨｮ [9, 13, 17]. * 04ｨ ｨ 06 ｨｰｨ ｨｪ02 ｨｪｨ 0708ｨｨ 00ｨｨ ｨｪｨ ｨｪ ｨｦ ｨｺ ｨｹ ｨｬ06ｨｦ 08ｨ ｨｬ06 ﾂ ｨｪ06ｨｦ ｨ ｨｬ ｨｬ ｨｦ 09ｨｺ ｨ ｨｺ ｨｰｨｮ Col la bo ra ti ve HIV and Anti-HIV Drug Resistance Network (CHAIN) , ｨ ｨｰｨ ｨｺ ｨｨｨｪｨｨ09ｨｰ020809ｨｰ09ｨ 06ｨ 08ｨ ｨ ｨｪｨｨ07 ｨｨ ｨｪｨ ｨｮｨｺｨｨ ｨｨｨｦ09ｨｺ06ｨｦ ｨ 02ｨｨｨｨ, ｨ 0302 ｨｪｨｨ , 8154 ｨｨ ISSN

2 ﾁ ｨｨ05ｨｹｨｪ ｨｨ07ｨｪｨｨ02 ｨｪｨ ｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ ｨｨ 05ｨｺ ｨｨ ｨｬ02ｨｦ 09ｨｰ 09ｨ ｨｬ02ｨｪ ｨｰ ｨｺｨ ｨ 02ｨｰ ｨｪｨ 05ｨｨ ﾂｨｨ ｨｪ06 ｨｪｨｮｨｺ ｨｰｨｨ01 - ｨｪ ｨｨ ｨｬ ｨｨ04 ｨｬ0609 (SNP) ｨｪｨ 01, 06ｨｰ 0902ｨｰ 09ｨｰ 0902ｨｪ ｨｪ ｨ ｨｺ06 01ｨｨ ｨ ｨｪｨｨ02 01ｨ ｨｪ ｨｪ ｨｬ02ｨｪ ｨｰ ｨｪｨｨ02 SNP ｨｪｨ ｨｨ ｨｨｨｰ ｨｮ 05ｨｹ ｨｰｨ ｨｰ02 ｨｰ06 ﾂｨｺ ｨｬｨｮ ｨｰｨ 02ｨｨｨｦ (04ｨ ｨｬ02 ｨｪｨ 0601 ｨｪ ｨ 0406 ｨｰｨｨ 09ｨｰ ｨｪ06 09ｨ ｨｪｨｨ ｨｮ 00ｨｨｨｬ), ﾂｨｰ06, ｨｺｨ ｨｺ 0708ｨ 09ｨｨ 0506, 0708ｨｨ090601ｨｨｨｰ ｨｺ ｨｨ04ｨｬ02ｨｪ02ｨｪｨｨ06 05ｨｺ ｨｨｨｨ ｨｨ 00ｨｮｨｪｨｺ02ｨｨ06ｨｪｨ 05ｨｹｨｪ06-09ｨｰｨｨ ｨｰ 0902ｨｰ 09ｨｰ 09ｨｮ 06 ｨｴｨｨ01 ｨｺ06 01ｨｨ 08ｨｮ 02 ｨｬ0401 ｨ 0205 ｨｺ ｨｪ0600ｨｨ02 ｨｨ ｨ ｨｰ0205ｨｨ ｨｮ ｨｰ 09ｨｪｨｨｨｬｨ ｨｪｨｨ ｨｨ09ｨｺｨｮ 0601ｨｪ06ｨｪｨｮｨｺ050206ｨｰｨｨ01ｨｪ ｨｨｨｬ060800ｨｨ04ｨｬ0609 (SNP) ｨｪｨ ｨｬ02ｨｪｨｰ ｨｬ02ｨｦ09ｨｰ09ｨ CYP450, ｨｺ06ｨｰ ｨｺｨ ｨ 06ｨｰ 0905ｨｨ07ｨｪｨｨ02 ｨｪｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ ｨｮｨｰ00ｨｬ ｨｨ04ｨｬ02ｨｪ02ｨｪｨｨ07 05ｨｺ ｨｨｨｨ ｨｨ ｨ ｨｺ - ｨｰｨｨ09ｨｪ0609ｨｰｨｨ ｨｬ02ｨｪｨｰ ｨ ｨｪｨｪ ｨｬ02ｨｦ09ｨｰ09ｨ. 00 ｨｰｨ ｨ 05ｨｨ ｨｰｨ ｨｪ04 ｨｪ02ｨｺ06ｨｰ ｨｨ ｨｰｨｪ0402 SNP ｨｪｨ ｨｬ02ｨｪｨｰ ｨｬ02ｨｦ09ｨｰ09ｨ CYP450, ｨｪｨ 0708ｨｨｨｬ0208 ｨｮ0302 ｨｮ09ｨｰｨ ｨｪ ｨｪ06, ﾂｨｰ06 00ｨ ｨｰｨｨ07 CYP2B6* ｨ ｨｪ 09 ｨｪｨｨ04ｨｺ06ｨｦ 05ｨｺ ｨｨ02ｨｦ CYP2B6 ｨ 0205ｨｺｨ, ｨｺ06ｨｰ0608ｨ ｨｨ090601ｨｨｨｰ ｨｺ ｨｮ090205ｨｨ ﾂ02ｨｪｨｨ06 ｨｺ06ｨｪ0202ｨｪｨｰ08ｨ 02ｨｨｨｨ 0500ｨ 09ｨｨ 0802ｨｪ 02ｨ 09 02ｨｨ ｨｰ ｨ 04 ｨｬ02 ｨｺ0502ｨｰ ｨｺｨｨ [1, 9, 13, 23, 26]. 00ｨ 03ｨｪ04ｨｬ 00ｨ ｨｺｨｰ060806ｨｬ ｨｮ ｨｪ0609ｨｰｨｨ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨ ｨｰ ｨｪｨｨ02 ｨｰｨ ｨｺ ｨｪｨ ｨ 02 ｨｬ06ｨｦ ｨｬｨｪ ｨｰ 0902ｨｪ ｨｪ06ｨｦ ｨｺｨ 0809ｨｰ0902ｨｪｨｪ06ｨｦ ｨｮ09ｨｰ06ｨｦ ﾂｨｨ090609ｨｰｨｨ ｨ ｨｪｨｨ04ｨｬｨ, ｨｰｨ ｨｴ02ｨｦ 0906ｨ 06ｨｦ 04ｨ ｨｴｨｨｨｰｨｪ04ｨｦ ｨｬ0201ｨ ｨｪｨｨ04ｨｬ, 09ｨｪｨｨ03ｨ 06ｨｴｨｨｨｦ 09ｨｪｨｮｨｰ08ｨｨｨｺ0502ｨｰ06 ﾂ - ｨｪｨｮ06 ｨｺ06ｨｪ 0202ｨｪ ｨｰ 08ｨ 02ｨｨ ｨｰ02ｨｪ 02ｨｨ ｨ 05ｨｹ ｨｪ06 ｨｰ06ｨｺ09ｨｨ ﾂ ｨｪ0401 ｨ 0002ｨｪ ｨｰ ｨｨ0806ｨｺ ｨｺｨｰ08ｨ 01ｨｨｨｬｨｨ ﾂ0209ｨｺｨｨ ｨｴ0209ｨｰ09 (ｨｺ0902ｨｪ06ｨ ｨｨ06ｨｰｨｨ - ｨｺ0609), 09ｨｺ0506 ﾂｨ ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ ｨｪｨｮｨｰ 08ｨｨ ｨｺ0502 ｨｰ06 ﾂ ｨｪ04ｨｬ 00ｨ ｨｺ ｨｰ0608ｨ ｨｬ, 0802 ｨ 05ｨｨ 04ｨｮ 06 ｨｴｨｨｨｬ 01ｨ ｨｪ - ｨｪ04ｨｦ ｨｬ0201ｨ ｨｪｨｨ04ｨｬ, 06ｨｰｨｪ060907ｨｰ0907 ｨｰ08ｨ ｨｪ ｨｰｨｪ04ｨｦ ｨ ｨｺ ｨｬｨｪ ｨｰ 0902ｨｪ ｨｪ06ｨｦ 0502 ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ06ｨｦ ｨｮ09ｨｰ06ｨｦ ﾂｨｨ ｨｰｨｨ (MDR) P-0005ｨｨ - ｨｺ ｨｰ02 ｨｨｨｪ (04-gly cop ro te in, P-gp). P-gp 0708ｨｨ ｨｪｨ ｨｨｨｰ ｨｺ ｨ 06 05ｨｹ 0306 ｨｬｨｮ 0902 ｨｬ02ｨｦ 09ｨｰ 09ｨｮ ABC-ｨｰ08ｨ ｨｪ ｨｰ ｨｪ0401 ｨ 0205 ｨｺ0609, ｨｰｨ 0902 ｨｺ06 ｨｰ ｨｨｨｬ02 02ｨｰ 0907 ABCB ｨｨ 08ｨｮ 02ｨｰ 0907 P-gp ｨｮ ﾂ ｨｺｨ 0002 ｨｪ06ｨｬ MDR1, ｨｺ06 ｨｰ ｨｦ 06ｨｰ 05ｨｨ ﾂｨ 02ｨｰ ｨ ｨｬ02ｨｰ ｨｪ04ｨｬ ｨｨ - ｨｬ ｨｨ04 ｨｬ06ｨｬ. 06ｨ ｨｺ, ｨｪｨ 0708ｨｨ ｨｬ0208, ｨｨ ｨｬ ｨｨ04ｨｬ C3435T (04ｨ ｨｬ02 ｨｪｨ 02ｨｨｨｰ0604ｨｨ ｨｪｨ ｨｪｨ ｨｰｨｨ ｨｬｨｨｨｪ) ｨｬ 05ｨｺ 0406 ｨｪ ｨｪｨ MDR1, ｨｮ 05ｨｹ ｨｰｨ - ｨｰｨ ｨｬ ｨｪ02 ｨｺ06 ｨｰ ｨ ｨ 06 ｨｰ, ｨ ｨｨ ｨｨ ｨ ｨｪ 09 00ｨ 08 ｨｬｨ ｨｺ06 ｨｺｨｨ ｨｪ02 ｨｰｨｨ - ｨｺ06ｨｦ ｨｨｨｪ00ｨｨｨ ｨｨｨｰ0608ｨ ｨｰ02ｨ 0404 (0603) 0006 ﾁ-1 ｨｪ020500ｨｨｨｪｨ 09ｨｨ08ｨ. 0308ｨｨ ｨｪｨ 05ｨｨ ﾂｨｨｨｨ 04ｨ ｨｬ02ｨｪ04 05 ｨｪｨ ｨｨ ｨｨｨｰ ｨｮ090205ｨｨ ﾂ02ｨｪｨｨ02 05ｨｺ ｨｨｨｨ ｨ 0205ｨｺｨ, ﾂｨｰ ｨ 03ｨ 02ｨｰ ｨｪｨｨ0302ｨｪｨｨ02ｨｬ ｨｺ06ｨｪ0202ｨｪｨｰ08ｨ 02ｨｨｨｨ ｨ 08ｨ ｨｰｨ 09 02ｨｨｨｰ060705ｨ 04ｨｬ ｨｬｨｪ0600ｨｨ01 08ｨ ｨ 06ｨｰｨ 01 06ｨｰｨｬ02- ﾂｨ 06ｨｰ, ﾂｨｰ06 01ｨ ｨｪ ｨｪ04ｨｦ 09ｨｨ ｨｨ ｨｬ ｨｨ04 ｨｬｨ ｨｨｨｬ02 02ｨｰ 0905ｨ ｨ 0602 ｨｪ02-08ｨ 09 ｨｪ ｨｪ ｨｪ ｨｨ ｨｮ ｨｬ ｨｮ 00ｨｨ ｨｬｨｨ SNP ｨ 0205 ｨｺｨ P-gp ｪ G2677T ｨｨ C1236T [7, 20, 23, 25]. 06ｨ ｨｺ 0302 ｨｺｨ ｨｺ ｨｨ P-gp, 0108ｨｮ 00ｨｨ02 ｨｰ08ｨ ｨｪ ｨｰ ｨｪ0402 ｨ 0205 ｨｺｨｨ ｨｬｨｪ ｨｰ 0902ｨｪ ｨｪ06ｨｦ 0502 ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ06ｨｦ ｨｮ09ｨｰ06ｨｦ ﾂｨｨ ｨｰｨｨ, 09 ﾂｨ 09ｨｰ ｨｪ06 09ｨｰｨｨ MRP, ｨｬ06 00ｨｮｨｰ ｨｰｨｹ ｨｪｨｨ04 ｨｺｨｮ06 ｨｰ02 08ｨ ｨｰｨｨ ﾂ02 09ｨｺｨｮ06 ｨｺ06ｨｪ ｨｪ ｨｰ 08ｨ 02ｨｨ ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ ｨ 0708ｨｨ ｨｬ0208, ｨｮ 07ｨ - 02ｨｨ02ｨｪｨｰ0609, ｨｮ ﾂｨ 06ｨｴｨｨ ｨｨ ｨｨｨｬ0206ｨｴｨｨ01 ｨｪｨｨ04ｨｺｨｮ06 05ｨｺ ｨｨ06 MRP1, 06ｨ ｨｪｨ 08ｨｮ 03ｨｨ 05ｨｨ ｨ ｨｺｨｮ06 09ｨｪｨｮｨｰ 08ｨｨ ｨｺ ｨｰ06 ﾂ ｨｪｨｮ06 ｨｺ06ｨｪ 0202ｨｪ ｨｰ 08ｨ 02ｨｨ06 08ｨｨ ｨｰ06 ｨｪｨ 09ｨｨ 08ｨ ｨｨ 09ｨ ｨｺ 09ｨｨ ｨｪｨ 09ｨｨ 08ｨ, ﾂ02ｨｬ ｨｮ 07ｨ 02ｨｨ02ｨｪｨｰ ｨｺ06ｨｦ 05ｨｺ ｨｨ02ｨｦ MRP1 [7, 25]. 06ｨ ｨｺｨｨｨｬ 06ｨ 08ｨ 0406ｨｬ, 0002 ｨｪ02 ｨｰｨｨ ﾂ02 09ｨｺｨ 07 09ｨ 08ｨｨ ｨ ｨ 02 05ｨｹ ｨｪ0609ｨｰｨｹ ｨｨ 00ｨｮｨｪ - ｨｺ 02ｨｨ 06 ｨｪｨ 05ｨｹ ｨｪ0609ｨｰｨｹ ｨｨ ｨｬ ｨｨ04 ｨｬ0609 ｨｮ ABC- ｨｨ MRP-ｨ 0205 ｨｺ0609, ｨ ｨｰｨ ｨｺ 0302 ｨｬ02 ｨｰｨ ｨ 06 05ｨｨ 04ｨｨ 08ｨｮ 06 ｨｴｨｨ ｨｬ02ｨｪ ｨｰ0609, ｨｺｨｮ07 ｨｪ06 09ｨｰｨｨ 06ｨｰ 08ｨ 03ｨ 0709ｨｹ ｨｪｨ 09ｨ 08ｨｨ ｨ ｨｰｨｨ09 ｨｪ06 09ｨｰｨｨ 0502 ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨｰ 0902 ｨｰｨ, 06ｨｺｨ ｨ 02ｨｰ 09ｨｨ 05ｨｹ ｨｪ ｨｨ 07 ｨｪｨｨ02 ｨｪｨ ｨｺｨｰ 0708ｨｨ ｨｬ02 ｨｪ02 ｨｪｨｨ07 ｨ ｨｪ - ｨｰｨｨ 0802ｨｰ ｨｨ 08ｨｮ09 ｨｪ ｨ 08ｨ ｨｰ ｨ ｨｺ02ｨｨ07 00ｨｨ ﾂｨｮ0909ｨｰ09ｨｨｨｰ0205ｨｹｨｪ0609ｨｰｨｨ 0201ｨｪ06 ｨｨ04 ｨｰ ｨｪ02ｨｪｨｨｨｦ, 09 ｨｺ06ｨｰ060804ｨｬ 0708ｨｨ010601ｨｨｨｰ ｨｰｨ 05ｨｺｨｨ09ｨ ｨｰｨｹ ｨｨ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨｨｨ ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪ ｨ 08ｨ ｨｰ0609, ｪ 0802 ｨ ｨｺ 02ｨｨ07 00ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｨ (0401 ﾁ), ｨｺ06 ｨｰ06 08ｨ ｨｨ ｨｪｨｪ0401 ｨｮ ｨｨ 0701 ｨｬ ｨｰ 0708ｨｨ ｨｰｨｨ ｨｺ 09ｨｬ0208ｨｰｨｨ 07ｨ 02ｨｨ02ｨｪｨｰｨ. 00 ｨｰ0208ｨ ｨｰｨｨ ﾂ0209ｨｺ06ｨｦ 0708ｨ ｨｺｨｰｨｨｨｺ ｨｨ09ｨ ｨｪ06, 0706 ｨｺ08ｨ ｨｦ ｨｪ02ｨｦ ｨｬ , 0109ｨ 09ｨｨ 01ｨ 0401 ﾁ ｪ ｨｺ ｨ 08ｨ ｨｰｨ ｨｬ 00ｨ ｨ ｨ ｨｺｨ - 09ｨｨ0803 ｨｨ ｨｮ ｨｪｨｮｨｺ ｨｨ01ｨｪ0401 ｨｨｨｪ00ｨｨｨ ｨｨｨｰ ｨ 08ｨ ｨｰｨｪ06ｨｦ ｨｰ08ｨ ｨｪ09ｨｺ08ｨｨ07ｨｰｨ 0404 (0206) ( ) ｨｨ 00ｨｪ0209ｨｨ08ｨ 07ｨｨｨｪ03 ｨｨ ｨｮ ｨｪ02 ｨｪｨｮｨｺ ｨｨ01 ｨｪ0401 ｨｨｨｪ 00ｨｨ ｨ ｨｨ ｨｰ ( ) ｨ ｨ 06 ｨｰｨ 01 ｨｬｨｪ06 00ｨｨ01 ｨｨ ｨ ｨｰ ｨｦ ｨ ｨｺｨ 04ｨ ｨｪ06, ﾂｨｰ ﾁ ｨｺ 05ｨｰｨｨｨｬ ｨ 08ｨ ｨｰｨ ｨｬ ｨｨｨｬ0202ｨｰ ｨｹ ｨ 02ｨｪｨｪ0609ｨｰ07ｨｬｨｨ ｨｪ06ｨｬｨ ｨｨｨｪｨ. 0308ｨｨｨｬ020806ｨｬ ｨｬ060302ｨｰ 0905ｨｮ03ｨｨｨｰｨｹ ｨ 05ｨｨ - ｨｰ0205ｨｹ ｨｪ04ｨｦ 02ｨｨ ｨｰ06 ｨｺｨｨｨｪ ｪ 00ｨ ｨｺ ｨｰ0608 ｨｪ02 ｨｺ ｨ 0607ｨｮ ｨｨ (TNF-1 7), 06ｨｺｨ ｨ 06ｨｴｨｨｨｦ 0905ｨｨ07ｨｪｨｨ02 ｨｪｨ 05ｨｨ07ｨｨ01ｨｪ04ｨｦ ｨｬ02ｨｰｨ ｨ 0605ｨｨ04ｨｬ, ｨｺ06ｨ 00ｨｮ ｨｨ06, ｨｮ09ｨｰ06ｨｦ ﾂｨｨ090609ｨｰｨｹ ｨｺ ｨｨｨｪ09ｨｮ05ｨｨｨｪｨｮ, 00ｨｮｨｪｨｺ02ｨｨ06ｨｪｨｨ080609ｨ ｨｪｨｨ02 05ｨｪ0106ｨｰ0205ｨｨ07 ｨｨ ｨ ｨｺｨｰｨｨ09ｨｨ08ｨｮ06ｨｴｨｨｨｦ ｨｪ04ｨｦ ｨｰ08ｨ ｨｪ09ｨｺ08ｨｨ0702ｨｨ06ｨｪ - ｨｪ04ｨｦ 00ｨ ｨｺ ｨｰ0608 NF-kB. 02ｨｺｨ 04ｨ ｨｹ, ﾂｨｰ ｨｨ ｨｬ ｨｨ04ｨｬ ｨｪ02 TNF-1 7 ｨ ｨｨｨｨ080609ｨ ｨｪ 09 00ｨｨ ﾂｨｮ0909ｨｰ09ｨｨｨｰ0205ｨｹｨｪ0609ｨｰｨｹ06 ｨｺ ｨ ｨ ｨ ｨｺｨ 09ｨｨ 08ｨｮ ｨｮ ｨｰｨ 09ｨｨ ｨｰ ｨｦ ｨｪ ｨｨ01 ｨｪ06ｨｦ 08ｨ 0904 [21]. 00ｨｪ06 00ｨｨ02 ｨｨ ｨ ｨｰ02 05ｨｨ ｨｪｨ ｨｰ ｨｹ 0401 ﾁ 09 ﾂ ﾂ02 09ｨｺｨｨ ｨｬｨｨ 0502ｨｦ ｨｺ06 02ｨｨ ｨｰｨ 08 ｨｪ04 ｨｬｨｨ ｨ ｨｪ ｨｰｨｨ 0002 ｨｪｨ ｨｬｨｨ (HLA), ｨｺ06 ｨｰ ｨｺ06 01ｨｨ 08ｨｮ 06ｨｰ ｨｮ ｨｦ 0002 ｨｪ0609 ﾂ ﾂ02 09ｨｺ ｨｺ06ｨｬ ｨｺ 09ｨ 00ｨｨ - 09ｨｰ ｨｬ0209ｨｰｨｨｨｬ0609ｨｰｨｨ (MHC) ｨｨ ｨｪ0706ｨｰ 00ｨｮｨｪｨｺ02ｨｨ06 08ｨ ｨｪｨ 09ｨ ｨｪｨｨ07 ﾂｨｮ ｨｪ ｨｨ ｨ ｨ 09ｨｰ 0902ｨｪ ｨｪ0401 ｨ ｨｪ ｨｰｨｨ 0002 ｨｪ0609, ｨｨ00 08ｨ 06 ｨｴｨｮ06 09ｨ 03 ｨｪｨｮ ｨｹ 09 ｨ ｨｺ ｨｰｨｨ 09ｨ 02ｨｨｨｨ ｨｨｨｬ ｨｬｨｮｨｪ ｨｪ ｨｰ 0902 ｨｰｨ ｨｪ02 ｨｰｨｨ ﾂ02 09ｨｺｨｨ02 09ｨ 08ｨｨ ｨ ｨｪ ｨｰ04 ｨｨ ｨｬ02ｨｪ ｨｰ ｨｬ02ｨｦ 09ｨｰ 09ｨ CYP450, ｨ ｨｨ ｨｨ ｨ ｨｪ ｨｪ ｨｪ02 ｨｪｨｨ 07 ｨｬｨｨ, ｨｪｨｨ ｨｺｨ 06 ｨｴｨｨ ｨｬｨｨ 0708ｨｨ ｨ ｨ 05ｨｨ 02ｨ 0102ｨｪ SNP 06ｨｪ 0102ｨｪ ｨｰｨｨ 00ｨｨ ｨｺｨ 02ｨｨ 06ｨｪ ｨｪ04ｨｦ ｨｪ06 ｨｬ0208 SNP 0902 ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ04ｨｦ ｨ 08ｨ ｨｰ 08ｨ 08ｨｬ0601ｨｨｨｪｨ ｨｬｨｨｨｺｨ CYP2B6 G516T rs ｨｨ 08ｨ 07ｨｨｨｪ 0402 ｨ ｨｺ 02ｨｨ07 00ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｨ CYP3A4*1B / CYP3A5*1 0600ｨ 09ｨｨ 0802ｨｪ ｨｨ ｨｨ ﾂ02 09ｨｺｨ 07 ｨｪ02ｨｦ ｨ ｨｰｨｨ07 T983C rs ｨｨ 08ｨ 07ｨｨｨｪ 0402 ｨ ｨｺ 02ｨｨ07 00ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｨ 0600ｨ 09ｨｨ 0802ｨｪ02 06ｨｪ 01ｨｨ ｨｪｨ 09ｨｨ ｨｨ ｨｨ ﾂ0209ｨｺｨ 07 ｨｪ02ｨｦ ｨ ｨｰｨｨ07 01ｨｨ ｨ ｨｨ 05ｨｨ 08ｨｮ ｨ ｨｨ ｨｪ02 ｨｬｨｨ ｨｨ ｨｰｨｨ ｨ 04 14

3 ｪ ｪ ｨ 05ｨｨ ﾂｨｨ02 ｨ HLA-B*5701 ｨｰ0209ｨｪ06 ｨ ｨｨｨｨ080609ｨ ｨｪ ｨ ｨｺ 02ｨｨ02ｨｦ 00ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｨ ｨｺ ｨ ｨ ｨ ｨｺｨ 09ｨｨ 08ｨｮ ｨｨ ｨｨ ｨｪ04ｨｬ ｨｨ 05ｨｨ ｨｨ01 ｨｪ06ｨｦ 08ｨ 0904; ｨｰ0802 ﾂｨ 02 - ｨｬ0609ｨｰｨｹ ｨｦ09ｨｺ06ｨｦ ｨｮ050702ｨｨｨｨ ｨｪ02ｨｬ ｨｰｨ ｨｰ 3 ｪ8% [26]. 06ｨｰ06ｨｰ 0708ｨｨ ｨｬ0208 ｨ ｨｺ ｨｰｨｨ09 ｨｪ06 06ｨ 09ｨｮ03 01ｨ ｨｨ ｨｰ02 08ｨ ｨｰｨｮ [18, 22] ｨｨ ｨｨ ﾂｨｨｨｰｨ 02ｨｰ 0907 ｨｪｨ ｨｨ ｨ ｨｮ01ｨ ﾂ ｨｪ04ｨｬ, ｨｰ.02. ｨｨｨｬ0206ｨｴｨｨｨｬ ｨｬｨ ｨｺ09ｨｨｨｬｨ 05ｨｹｨｪｨｮ ｨｪ0609ｨｰｨｨ ﾂ0209ｨｺｨｮ ｨｪｨｪ0609ｨｰｨｹ, 09 06ｨｰｨｪ060302ｨｪｨｨｨｨ ｨｪ02ｨｪｨｨｨｦ 0502 ﾂ02ｨｪｨｨ ﾁ-ｨｨｨｪ0002ｨｺ02ｨｨｨｨ. 01ｨ 0708ｨ ｨｺ ｨｰｨｨ ｨｺ02, ｨｮ0708ｨ ｨｪｨｨ ｨｺ06ｨｪ ｨｰ ｨｺｨ ﾂ02 09ｨｰ 09ｨ 07ｨｨ - ｨｴ ｨｮｨｺ ｨｰ0609 ｨｨ 0502 ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨ 08ｨ ｨｰ (FDA) ｨｺ06ｨｬ02ｨｪ01ｨｮ02ｨｰ ｨｨｨｰｨｹ ｨｰ0209ｨｰｨｨ080609ｨ ｨｪｨｨ02 07ｨ - 02ｨｨ 02ｨｪ ｨｰ0609 ｨｪｨ HLA-B* ｨｪｨ 04ｨｪｨ ﾂ02 ｨｪｨｨ 02ｨｬ ｨｰ02 08ｨ 07ｨｨｨｨ ｨ ｨ ｨ ｨｺｨ 09ｨｨ 0806ｨｬ, ﾂｨｰ06 09ｨｪｨｨ 03ｨ 02ｨｰ 08ｨｨ09ｨｺ 08ｨ 04 09ｨｨ ｨｰｨｨ ﾁ ｨｺ ｨ 08ｨ - ｨｰｨｮ ｨｨｨｨ 01ｨ ｨｪ ｨｪ0602 ｨｰ02 09 ｨｰｨｨ ｨ ｨｪｨｨ ｨｺ06 ｨｬ02ｨｪ ｨ ｨｪ (0308ｨｨ ｨｺｨ ｨ 09 ｨｪｨ ｨ 06ｨｰ ). 03ｨｴ ｨｪｨｨｨｬ 0708ｨｨｨｬ020806ｨｬ 0905ｨｨ07ｨｪｨｨ07 ｨｪｨ ｨｺｨｰ ｨｬ ｨｰ 0905ｨｮ 03ｨｨｨｰｨｹ ｨ ｨｹ ｨｪ04ｨｦ 09ｨ 08ｨｨ ｨ ｨｪｨｰ HLA-DRB1*0101, ｨｺ06 - ｨｰ ｨｦ, ｨｬ0603 ｨｪ06, ｨｰ 0907 ｨｨｨｬ ｨｬｨｮ ｨｪ ｨｪ02 ｨｰｨｨ ﾂ02 09ｨｺｨｨｨｬ ｨｬｨ 08ｨｺ000806ｨｬ 00ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｨ ｨｺ ｨｪ02 09ｨｨ 08ｨ 07ｨｨ ｨｪｨｮ, ｨｴ02ｨｦ0907 ｨｪ0209ｨｨ08ｨ 07ｨｨｨｪ ｨ ｨｪｨｪ04ｨｬｨｨ ｨ ｨｰｨｨｨｰｨ ｨｬｨｨ ｨｨ ｨｹ06 ｨｮ ｨｨ ｨｬ02 ｨ HLA-DRB1* ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｹ06 ｨｺ ｨｪ02 09ｨｨ 08ｨ 07ｨｨ ｨｪｨｮ ｨ 06ｨｰ 02ｨｴ00 ｨｪ02 09ｨｺ06 05ｨｹ ｨｺ06 ｨ ｨｦ: HLA-Cw*8, HLA-B*14, HLA-Cw*4, HLA-B*3505 [2, 14, 23, 26, 27]. 08ｨ ｨｺ 09ｨｨ01 ｨｪ06 ｨｨ ｨｨ ｨｪｨｪ ｨ ｨｪ ｨｪ0401, 0802 ｨ ｨｺ 02ｨｨ07 00ｨｨ ﾂｨｮ09 09ｨｰ 09ｨｨ ｨｰ02 05ｨｹ ｨｪ06 09ｨｰｨｨ ｨｨｨｬ02 02ｨｰ ｨ ｨｨ 05ｨｹ ｨｪｨｮ ｨｹ ｨ 02ｨｪ - ｨｪ06 09ｨｰ07 ｨｬｨｨ 0002 ｨｪ06 ｨｬｨ ｨｨ ｨｪｨ, ﾂ02ｨｬ 05ｨｰ ｨｰｨ ｨｹ 08ｨ ｨｪ ｨ ｨｺｨｨｨｬ 06ｨ 08ｨ 0406ｨｬ, 04ｨｪｨ ｨｪｨｨ ｨ ｨｪｨｪ06ｨｦ ｨ 02ｨｪｨｪ0609ｨｰｨｨ ｨｨ 0401 ﾁ ｨｪ ｨｪ04 ｨｬｨｨ 00ｨ ｨｺ ｨｰ06 08ｨ ｨｬｨｨ ﾂ ｨｺｨ 01ｨ 00ｨｰ ｨｬ0603 ｨｪ0609ｨｰｨｹ ｨｪｨ 0708ｨ ｨｺｨｰｨｨｨｺ02 09ｨｪｨｨ04ｨｨｨｰｨｹ ﾂｨｨ ｨｮ ﾂｨ ﾁ, ｨｪｨｨｨｺｨ 06ｨｴｨｨ01 ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ0401 ｨｨｨｪ01ｨｨ09ｨｨ01ｨｮｨｮｨｬ0609, ｨｪｨ ｨｴｨｨ ｨｪｨ ｨｨ ｨｨ 09ｨｰ ｨｨ07 09ｨｨ ｨｨ 09ｨｰ ｨｨ ｨｰｨ ｨｰ 0906 ｨ 06ｨｦ 0601 ｨｪ06 ｨｨ04 ｨｰ ｨｪ02ｨｪｨｨｨｦ, ｨｪｨｨｨｺｨ 06ｨｴｨｨ01 ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨ 02ｨｨ02ｨｪｨｰ ｨｨ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨｨｨ ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪ ｨ 08ｨ ｨｰ0609, 09ｨｺ0506 ﾂｨ 07 ｨｨｨｪ 00ｨｨ ｨ ｨｨ ｨｰ ｨｰ02 ｨ 0404, ｨｨ 01ｨ 08ｨ ｨｺ ｨｰ02 08ｨｨ 04ｨｮ 02ｨｰ , ｨｮ06 06 ﾂ ｨｹ, 0706 ｨｰ ｨｦ ｨｺ0603 ｨｪ06ｨｦ 03ｨｨ ｨｦ ｨｺ0502ｨｰ ﾂｨ ｨｰ ｨｺｨｨ 09 06ｨ 05ｨ 09 ｨｰｨｨ 05ｨｨ 02ｨ, 08ｨｮｨｺ ｨｨ ｨｪ ｨｪ02 ｨｺ06 ｨｰ ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨｨ02 05ｨｨ070601ｨｨ09ｨｰ080600ｨｨ07 ｨｬ060302ｨｰ ｨｰ02ｨｺｨ ｨｰｨｹ ｨｮｨｰ09ｨｰ09ｨｮ06ｨｴｨｨｨｬ 06ｨｰ ｨｪｨｨ02ｨｬ 05ｨｨ03ｨｪ ｨｨ08ｨ 09 06ｨ 05ｨ 09ｨｰｨｨ 0302ｨｨ ｨｨ ｨｪ02ｨｦ ﾂｨ 09ｨｰｨｨ 0907ｨｨｨｪ04, ﾂｨｰ ｨｨ090601ｨｨｨｰ ｨｺ 06ｨ - 08ｨ ｨ ｨｪｨｨ ｨｦｨｪ ｨ ｨｺｨ ｨｨ ｨ ｨｮ ｨｪｨ 0907ｨｨｨｪ02 ( ｨ ｨ ｨｮｨｦ ｨ 03). 09ｨｨ070601ｨｨ09ｨｰ080600ｨｨ07 08ｨ 0409ｨｨ09ｨ 02ｨｰ ｨｨｨｬ0208ｨｪ06 ｨｮ 40% 07ｨ 02ｨｨ - 02ｨｪ ｨｰ ｨｰ02 ﾂ02 ｨｪｨｨ ｨ ｨｪｨ ﾂｨ 05ｨ 0502 ﾂ02 ｨｪｨｨ07, ｨｨ ｨｬ04 ｨ ｨｪ ｨｰｨｨ 0802ｨｰ ｨｨ 08ｨｮ09 ｨｪ ﾂ02 ｨｪｨｨ07 09ｨｺ0506 ﾂ02 ｨｪ04 ｨｨｨｪ 00ｨｨ ｨ ｨｨ ｨｰ ｨｰ02ｨ ｨ ｨｺｨｨｨｬ 06ｨ 08ｨ 0406ｨｬ, 0708ｨｨ06ｨ 0802ｨｰ00ｨｪｨｪｨ 07 05ｨｨ070601ｨｨ09ｨｰ ｨｨ07 ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨｨ02, ｨｮ ﾂｨ 06ｨｴｨｨ , ｪ 03ｨｨ0806ｨｺ06 08ｨ ｨｰ08ｨ ｨｪ00ｨｪｨｪ ｨｪ02ｨｪｨｨ ｨｹ03ｨｨｨｪ09ｨｰ ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ0401 ｨｨｨｪ01ｨｨ09ｨｨ01ｨｮｨｮｨｬ ｨｨ070601ｨｨ09ｨｰ080600ｨｨ02ｨｦ ｨｬ0600ｨｮｨｰ 09 ﾂｨｨｨｰｨ ｨｰｨｹ ｨｰｨｪ0609ｨｨｨｰ0205ｨｹｨｪ ｨｬｨｨ, 0601ｨｪｨ ｨｺ06 ｨｪ ｨｺ06 06ｨｪｨ ｨ 02ｨｰ ｨｨ09ｨｰ02ｨｪｨｰｨｪ06-09ｨｰｨｹ06 ｨｺ ｨｨｨｪ09ｨｮ05ｨｨｨｪｨｮ, 00ｨｨ070208ｨｰ08ｨｨ0005ｨｨ020208ｨｨ0102ｨｬｨｨ02ｨｦ ｨｨ 09ｨｪｨｨ0302ｨｪｨｨ02ｨｬ ｨｮ080609ｨｪ07 ｨｺ06ｨｪ0202ｨｪｨｰ08ｨ 02ｨｨｨｨ 05ｨｨ ｨｰ02ｨｨｨｪ ｨｺ06ｨｦ ｨｰｨｪ06-09ｨｰｨｨ ｨ 04 ｨｬ02 ｨｺ ｨｨ. 08ｨ ｨｺ ｨｨ 0607ｨｨ 09ｨ ｨｪ ｨｪ ｨｰ ｨ ｨｪ ｨｪ02 ｨｪｨｨ07, 05ｨｨ ｨｨ 09ｨｰ ｨｨ07, ｨｺｨ ｨｺ 06ｨｺｨ 04ｨ ｨｹ, ｨｰ ｨｨｨｬ02 02ｨｰ ｨｹ ｨｪ06 ｨｬ06ｨｬ ﾂ ｨｺｨ. 06ｨ ｨｺ, ｨ ｨ ｨｬ02 ﾂ02ｨｪ06, ﾂｨｰ ｨｨｨｬ060800ｨｨ04ｨｬ T 0002 ｨｪｨ IL-11 7, ｨｺ0601ｨｨ08ｨｮ06ｨｴ ｨ 05ｨｨｨｰ0205ｨｹｨｪ04ｨｦ 02ｨｨｨｰ06ｨｺｨｨｨｪ ｪ ﾂ0502ｨｪ 0902 ｨｬ02ｨｦ 09ｨｰ 09ｨ ｨｨｨｪ ｨｰ ｨｦ ｨｺｨｨ ｨｪｨ 1, 09ｨｪｨｨ 03ｨ 02ｨｰ 08ｨｨ09ｨｺ 08ｨ 04 09ｨｨ - ｨｰｨｨ07 05ｨｨ070601ｨｨ09ｨｰ080600ｨｨｨｨ ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨ 02ｨｨ02ｨｪ - ｨｰ0609, ｨｪｨ ｨｴｨｨ ｨｪｨ ｨｨ 0708ｨｨｨｪｨｨｨｬｨ 06ｨｴｨｨ01, 09 ﾂｨ 09ｨｰｨｪ06-09ｨｰｨｨ, 09ｨｰｨ 09ｨｮ 01ｨｨｨｪ ｨｨ ｨｮ [6] ｨｨ ｨｬ ｨｨ04ｨｬ ｨｪｨ TNF ｨ 06ｨｰ 09 05ｨｨ070601ｨｨ09ｨｰ080600ｨｨ02ｨｦ, ｨｪ ｨｺ06 ｨｪｨ - ｨ ｨ 02 ｨｬ06ｨｦ ｨｮ 07ｨ 02ｨｨ 02ｨｪ ｨｰ ｨｨ01 ｨｪ06ｨｦ 08ｨ 0904, ｨｮ ﾂｨ 06 - ｨｴｨｨ01 09 ｨｺｨ ﾂ02 09ｨｰ ﾂ02 ｨｪｨｨ ｨ 08ｨ ｨｰ ｨｮ [21, 24]. 03ｨｴ ｨｨｨｪ 0002ｨｪ IL-18, ｨ ｨｨｨｨ080609ｨ ｨｪｨｪ04ｨｦ, 0706 ｨｬｨｪ02ｨｪｨｨ06 ｨｪ02ｨｺ06ｨｰ ｨ 09ｨｰ [10], 09 05ｨｨ070601ｨｨ09ｨｰ080600ｨｨ02ｨｦ, ｨｨｨｰ ｨｪ0209ｨｺ0605ｨｹｨｺ ｨｨｨｬ060800ｨｨ04ｨｬ0609, ｨｺ06ｨｰ ｨｺ06ｨｬｨ ｨｨｨｪｨ 02ｨｨｨｨ ｨ ｨｨｨｨ08ｨｮ06ｨｰ ｨ ｨｴｨｨｨｰｨｪ04ｨｬ ｨｺｨｰ06ｨｬ ｨｰｨｨ09 05ｨｨ070601ｨｨ09ｨｰ ｨｨｨｨ ｨｨ ｨｬ ｨｨ04 ｨｬ04 T455C, C482T ｨｨ C3238G 0002 ｨｪｨ APOC3, ｨｺ0601ｨｨ08ｨｮ06ｨｴ ｨ ｨｨ ｨｰ02ｨｨｨｪ 0705ｨ 04ｨｬ04 ｨｺ080609ｨｨ ｨｨ ｨｮ ｨｨ ｨｰ02ｨｨｨｪ0609 ｨｪｨｨ04ｨｺ06ｨｦ ｨｨ ｨｺ06ｨｦ ｨｰｨｪ0609ｨｰｨｨ, ｨｮ 05ｨｹ ｨｰｨ ｨｰｨ ｨｬ ｨｪ02 ｨｺ06 ｨｰ ｨｨ ｨ ｨｪｨｨｨｦ, 0708ｨｨ ｨｰ ｨｺ ｨｮ ｨｨ ﾂ02ｨｪｨｨ ｨ ｨｪｨｨ07 ｨｰ08ｨｨ0005ｨｨ020208ｨｨ ｨｺ080609ｨｨ 0708ｨｨ 0708ｨｨ - ｨｬ02ｨｪ02ｨｪｨｨｨｨ ｨ ｨｪｨｰｨｨ0802ｨｰ080609ｨｨ08ｨｮ09ｨｪ ｨ 08ｨ ｨｰ0609 ｨｨ ｨｮ , 09 ﾂｨ 09ｨｰ ｨｪ06 09ｨｰｨｨ 08ｨｨ ｨｰ06 ｨｪｨ 09ｨｨ 08ｨ ; 05ｨｰ06, ﾂ ｨｹ, ｨｮ ｨｨ ﾂｨｨ 09ｨ - 02ｨｰ 08ｨｨ09ｨｺ 05ｨｨ070601ｨｨ09ｨｰ080600ｨｨｨｨ ｨｨ ﾂｨｪ ｨｮ01ｨｨ09ｨｰ ｨ ｨ ｨ ｨｪｨｨｨｦ [8]. 01ｨ 05ｨｨ ﾂｨｨ02 05ｨｨ070601ｨｨ09ｨｰ080600ｨｨｨｨ ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ0401 ｨｨｨｪ01ｨｨ09ｨｨ01ｨｮｨｮｨｬ0609, ｨｪｨ ｨｴｨｨ ｨｪｨ , ｨ 06ｨｰ ｨｰｨ ｨｺ ｨｨｨｬ060800ｨｨ04ｨｬｨ ｨｬｨｨ 0002ｨｪ0609 Fas, ARb2, ARb3, HFE, LPIN1 ｨｨ05ｨｨ POLG [11, 15, 19, 28]. 0102ｨｦ080607ｨ ｨｰｨｨ ｨｺ06 ｨｮ 0006 ﾁ-ｨｨｨｪ 00ｨｨ 02ｨｨ ｨ ｨｪ ｨｪ ｨｨ02, ｨｪｨ ｨｴｨｨ ｨｪｨ , ｨｪｨ ｨ ｨ 06ｨｰ ｨ 0405ｨｨ ﾂｨｪ ｨｪ02ｨｪｨｨ ｨｰ ｨｪ04 ｨｪ020809ｨｪ06ｨｦ 09ｨｨ09ｨｰ02ｨｬ04; 0708ｨｨｨｬ020806ｨｬ ｨｬ060302ｨｰ 0905ｨｮ03ｨｨｨｰｨｹ ｨｨ000208ｨｨ ﾂ0209ｨｺｨ 07 ｨｪ02ｨｦ080607ｨ ｨｰｨｨ ｨｨ000208ｨｨ ﾂ0209ｨｺｨ 07 ｨｪ02ｨｦ ｨ ｨｰｨｨ07 ｪ 05ｨｰ ｨｰ06 07 ｨｪｨｨ02, ｨ ｨｪ ｨｪ ｨｪｨｨ 02ｨｬ 0601 ｨｪ ｨｨ05ｨｨ ｨｪ02-09ｨｺ0605ｨｹ ｨｺｨｨ ｨｨ ｨｨ ﾂ02 09ｨｺｨｨ01 ｨｪ , 0708ｨｨ ｨｴ0202 ｨｺ ｨｪｨ 08ｨｮ ｨｪｨｨ06 06ｨ ｨｬ02ｨｪｨ 09ｨｨ00ｨｪｨ 05ｨ ｨｬｨｨ ｨｬ020301ｨｮ 0202ｨｪｨｰ08ｨ 05ｨｹｨｪ06ｨｦ ｨｨ ｨｨ ｨｨ ﾂ0209ｨｺ06ｨｦ ｨｪ020809ｨｪ04ｨｬｨｨ 09ｨｨ09ｨｰ02ｨｬｨ ｨｬｨｨ. 05ｨｨｨｬ07ｨｰ06ｨｬ ｨｨ000208ｨｨ ﾂ0209ｨｺ06ｨｦ ｨｪ02ｨｦ080607ｨ ｨｰｨｨｨｨ 08ｨ 0409ｨｨ09ｨ 06ｨｰ ｨｰ020702ｨｪｨｪ06 ｨｨ ｨｬ ｨｪｨｪ ｨｨ08ｨｮ06ｨｰ; ﾂｨ ｨｴ , 07ｨ 02ｨｨ02ｨｪｨｰ04 ｨｨ090704ｨｰ0409ｨ - 06ｨｰ 0706 ｨｺｨ ｨ ｨｪｨｨ02 ｨｨ 06ｨｪ02 ｨｬ02 ｨｪｨｨ02, ｨｺ06 ｨｰ ｨｪｨ ﾂｨ 05ｨ ｨｪｨ ﾂｨｨ ｨｪｨ - 06ｨｰ ｨｺｨｨ 09 ｨｰ ｨｮｨｺ ｨｨ 09ｨｰ06 07ｨ 01, ｨ 04ｨ ｨｰ02ｨｬ 08ｨ ｨｰ08ｨ ｨｪ07 06ｨｰ 0907 ｨｪｨ ｨｰ ｨｰ06ｨｰ 09ｨｨ ｨｪ02ｨｪｨｨｨｦ ﾂｨ ｨｴ ｨ 06ｨｰ ｨ 06 ﾂ - ｨｪ04ｨｬ ｨｺ ｨｰ06ｨｬ ｨ 08ｨ ｨｰ ｨｮ , 0708ｨｨ 05ｨｰ06ｨｬ ｨｬｨｪ06 00ｨｨ02 ｨｨ ｨ ｨｪｨｨ07 06ｨ ｨｪｨ 08ｨｮ 03ｨｨ 09ｨ 06ｨｰ ｨｹ ｨｬ ｨｮ ｨｨ ｨｨ ﾂ02 09ｨｺ06ｨｦ ｨｪ02ｨｦ ｨ ｨｰｨｨ02ｨｦ ｨｨ 0002 ｨｪ06 ｨｬ06ｨｬ ﾂ ｨｺｨ. 06ｨ ｨｺ, 0708ｨｨ 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨｨｨ 09ｨｰｨ 09ｨｮ01ｨｨｨｪｨ ｨｨ ｨｨ ｨｪ0401 ｨｮ 0006 ﾁ-ｨｨｨｪ 00ｨｨ 02ｨｨ ｨ ｨｪ ｨｪ ｨ 02ｨｨ 02ｨｪ ｨｰ0609, ｨｪ06 ｨｬ02 ｨｺ06 ｨｰ ｨｨｨｬ0206ｨｰ ｨｨｨｬ060800ｨｨ04ｨｬ04 C2890T ｨｨ A3428G 0002ｨｪｨ POLG ｨｬｨｨｨｰ060106ｨｪ0108ｨｨｨ 05ｨｹｨｪ06ｨｦ , ｨｺ0601ｨｨ08ｨｮ06ｨｴ ｨｬｨｨｨｰ060106ｨｪ0108ｨｨｨ 05ｨｹｨｪｨｮ ｨｨ ｨｬ02 08ｨ 04ｨｮ, ｨｪｨ ｨ ｨ 02ｨｰ ｨｨ09ｨｺ 08ｨ 04 09ｨｨ ｨｰｨｨ ｨｨ000208ｨｨ ﾂ0209ｨｺ06ｨｦ ｨｪ02ｨｦ080607ｨ ｨｰｨｨｨｨ [3]. ISSN

4 ﾁ ｨｨｨｬ060800ｨｨ04ｨｬ04 G516T ｨｨ C983T ｨｪ02, ｨｺ0601ｨｨ08ｨｮ06ｨｴ02ｨｬ ｨｬ02ｨｰｨ ｨ 0605ｨｨ ﾂ0209ｨｺｨｨｨｦ ｨｨ ｨｬ02ｨｪｨｰ CYP2B6, ｨ ｨｨｨｨ080609ｨ ｨｪ ｨｨ05ｨｹｨｪ04ｨｬ ｨｪｨｨ02ｨｬ 08ｨｨ09ｨｺｨ ｨｪｨｨ ｨｨ000208ｨｨ ﾂ0209ｨｺ06ｨｦ ｨｪ02ｨｦ080607ｨ ｨｰｨｨｨｨ ｨｮ 07ｨ 02ｨｨ02ｨｪｨｰ0609, ｨｮ ﾂｨ 06ｨｴｨｨ ｨ 09ｨｨ0802ｨｪ02. 08ｨｪｨ ｨｨ ﾂｨｪ ｨｪｨｨ ﾂ02ｨｪｨｨ ｨ 09ｨｨ0802ｨｪ0202ｨｬ ｨ 06ｨｰ 09 ｨｪｨ 05ｨｨ ﾂｨｨ02ｨｬ ｨｨｨｬ060800ｨｨ04ｨｬｨ C3435T 0002ｨｪｨ MDR1 [16]. 0208ｨｮ 00ｨｨ ｨｪ02 ｨｪｨｨ ｨｨｨｪ ｨｰ ｨｨ ｨ ｨｰ ｨｦ ｨｨ ｨｪ02 - ｨｪｨｨｨｦ, 0909ｨｰ0802 ﾂｨ 06ｨｴｨｨ ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨ 02ｨｨ02ｨｪ - ｨｰ0609, ｨｮ ﾂｨ 06 ｨｴｨｨ ｨｨ 00ｨｨ ﾂ02 09ｨｺ ﾂ02 ｨｪｨｨ02, ｨｪｨ ｨｨｨｰ 0907 ｨｰｨ ｨｺ ｨｨ070208ｨ ｨｨ05ｨｨ08ｨｮｨ ｨｨｨｪ02ｨｬｨｨ07 ｪ ｨｰ0607ｨｪｨｨ02, 01ｨ 08ｨ ｨｺｨｰ0208ｨｨ04ｨｮ02ｨｬ0602 ｨｮ ｨｨ ﾂ02ｨｪ ｨｪ04ｨｬ ｨｺ06 05ｨｨ ﾂ02 09ｨｰ 0906ｨｬ ｨｰ ｨｺ02 ｨｺ ｨｨ ﾂｨｪ ｨｨ00ｨｬ02ｨｪｨｰｨ ｨ ｨｨ05ｨｨ08ｨｮｨ ｨｨｨｪｨ ｨｬ02ｨｪｨｰ UGT1A1 ｨｰ08ｨ ｨｪ ｨｬｨｨ 08ｨｮ 02ｨｰ ｨｪ02 ｨ 06 05ｨｹ 03ｨｨ02 05ｨｨ ｨｨ 05ｨｹ ｨｪ0402 ｨｬ ｨｺｨｮ 0504, ｨｰｨ ｨｺｨｨ02, ｨｺｨ ｨｺ ｨ ｨｨ 05ｨｨ 08ｨｮ ｨ ｨｨｨｪ, 09ｨｰ ｨｨ 0104, ｨｬ06 ｨｪ04, 0502 ｨｺｨ 08 09ｨｰ 0902ｨｪ ｨｪ ｨｴ02 09ｨｰ 09ｨ, ｨ 09ｨｰ ｨｨ ｨｬｨｮ ｨｬｨｮ, 0708ｨｨ000601ｨｪｨｮ ｨ 05ｨｹｨｪ02ｨｦ0302ｨｦ 05ｨｺ09ｨｺ080202ｨｨｨｨ. 02ｨｪ 06ｨｺｨ ｨ 02ｨｰ 0905ｨｨ 07 ｨｪｨｨ02 ｨｨ ｨｪｨ ｨｰ06ｨｺ09ｨｨ ﾂ ｨｪ0609ｨｰｨｹ ｨ ｨｪ ｨｰｨｨ 0802ｨｰ ｨｨ 08ｨｮ09 ｨｪ ｨ 08ｨ ｨｰ0609 ｪ ｨ ｨｰｨ 04ｨ ｨｪｨ 09ｨｨ 08ｨ, ｨｨｨｪ 01ｨｨ ｨｪｨ 09ｨｨ 08ｨ ｨｨ ｨｮ ｨｨｨｪ 00ｨｨ - ｨ ｨｨ ｨｰ ｨｰ02 ｨ 04, ｨｨ ｨｪｨ ｨｮ ｨｪｨｹ ｨ ｨｨ 05ｨｨ 08ｨｮ ｨ ｨｨ ｨｪｨ 09 ｨｺ ｨｨ ｨｮ 0006 ﾁ-ｨｨｨｪ 00ｨｨ 02ｨｨ ｨ ｨｪ ｨｪ ｨ 02ｨｨ 02ｨｪ ｨｰ ｨ ｨｺ ｨ ｨ ｨｪｨ 08ｨｮ ｨｪ06, ｨｪｨ 05ｨｨ ﾂｨｨ02 ｨ UGT1A1*28, ｨ ｨｪｨｪ ｨｪｨｨ0302ｨｪｨｨ - 02ｨｬ ｨｰ08ｨ ｨｪ09ｨｺ08ｨｨ0702ｨｨｨｨ 01ｨ ｨｪｨｪ ｨｬ02ｨｪｨｰｨ, ｨ 02ｨｰ 08ｨｨ09ｨｺ 08ｨ 0409ｨｨｨｰｨｨ07 00ｨｨ070208ｨ ｨｨ05ｨｨ08ｨｮｨ ｨｨｨｪ02ｨｬｨｨｨｨ [23, 26, 27]. 07 ｨｨｨｪ01ｨｨ09ｨｨ01ｨｮｨｮｨｬ0609, ｨｮ ﾂｨ 06ｨｴｨｨ , 0708ｨｨ ｨｪｨ 05ｨｨ ﾂｨｨｨｨ ｨ HLA-A*68 ｨｪｨ ｨ ｨ 02ｨｰ ｨｺｨｨｨｦ 08ｨｨ09ｨｺ ｨ 09ｨｰ ｨｬｨ ｨｰｨｨ ﾂ02-09ｨｺｨｨ ｨｪ02 ｨｪｨｨｨｦ, 09 ｨｰ ｨｬ07 ｨｺｨ ｨｺ ｨｮ 05ｨｨ02, ｨｨｨｬ02 06 ｨｴｨｨ01 ｨ ｨｹ HLA-Cw*6, 03ｨ ｨｪ ｨｮ ﾂｨｨｨｰｨｹ ｨ 09ｨｰ ｨｬｨｮ ｨｪｨ ｨｬｨｪ ｨｪｨｨ 0302 [12]. 0208ｨｮ ｨｪ02 ｨｪｨｨ02 ｪ ｨｪ02ｨｦ ｨｰ ｨｪｨｨ07 ｪ 01ｨ 08ｨ ｨｺ ｨｰ02 08ｨｨ 04ｨｮ - 02ｨｰ0907 ｨｮ ｨ 06ｨｴｨｨｨｬ 03ｨｨ04ｨｪｨｨ ｨｰ0607ｨｪｨｨ02ｨｬ 09 09ｨｨ0102 ｨ 0409ｨｰ ｨｪｨｨ0302ｨｪｨｨ07 ﾂｨｨ0905ｨ 02ｨｨ08ｨｺｨｮ05ｨｨ08ｨｮ06ｨｴｨｨ01 09 ｨｺ080609ｨｨ ｨｪ02ｨｦｨｰ080600ｨｨ050609; ｨｮ 05ｨｹ ｨｰｨ ｨｰｨ ｨｬ ｨｪ02 ｨｺ06 ｨｰ ｨｪｨｪ0401 ｨｨ ｨ ｨｪｨｨｨｦ ｨｪ02ｨｦｨｰ ｨｪｨｨ07 ｨ ｨｨｨｨ08ｨｮ02ｨｰ ｨｨｨｬ060800ｨｨ04ｨｬ06ｨｬ A1203A (rs ) 0002 ｨｪｨ MRP4 [4]. 07 ｨｰｨ ｨｺ ｨｪ02 ｨｪｨｨ07, ｨｺｨ ｨｺ 01ｨｨ09 05ｨｨ 07ｨｨ 0102 ｨｬｨｨ07, 01ｨ 08ｨ ｨｺ ｨｰ02 08ｨｨ - 04ｨｮ06ｨｴ ｨｪｨｨ02ｨｬ ｨ ｨｪｨｨ07 05ｨｨ07ｨｨ ｨｺ080609ｨｨ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ ｨ 02ｨｨ02ｨｪｨｰ0609, 0708ｨｨｨｪｨｨｨｬｨ 06ｨｴｨｨ01 08ｨｨ - ｨｰ06 ｨｪｨ 09ｨｨ08, ｨｬｨｪ06 00ｨｨ02 ｨｨ ｨ ｨｰ02 05ｨｨ ｨｪｨ ｨｰ ｨｹ ｨｮ ｨｦ 0002 ｨｪ0609 ﾂ ｨｺｨ : ABCA1, APOA5, APOC3, APOE ｨｨ CETP [5, 19]. 05ｨ ｨｺ0506 ﾂ02 ｨｪｨｨ02 08ｨ ｨｺ 09ｨｨ01 ｨｪ06 ｨｨ04 01ｨ ｨｪ ｨｪ ｨｰ ｨｺ08ｨ ｨｰ ｨｺ ｨ ｨ, 09 ｨｺｨ ｨｬ ｨｬ 09ｨｰｨ ｨｪ06 09ｨｨｨｰ ﾂ02 09ｨｨ01 ｨｪ0202 ｨｪｨ 05ｨｨ ﾂｨｨ02 09ｨｨ 05ｨｹ ｨｪ06ｨｦ ｨｨ ｨｬ020301ｨｮ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｹ ｨｨｨｬ02ｨｪ02ｨｪｨｨ ｨｮ 0006 ﾁ-ｨｨｨｪ00ｨｨ02ｨｨ080609ｨ ｨｪｨｪ0401 ｨｨｨｪ01ｨｨ09ｨｨ01ｨｮｨｮｨｬ0609 ｨｨ ｨ 02ｨｪｨｪ0609ｨｰ07ｨｬｨｨ 0002 ｨｪ06 ｨｬｨ ﾂ ｨｺｨ, ﾂｨｰ ｨｰ ｨｨｨｰｨｹ ｨｪｨｨｨｨ 09 09ｨｺ ｨｬ ｨｬ02 ｨｪｨｨ ｨｪ ｨｬ02 ｨｰ ｨｪ06 04ｨｨ ｨ ｨｪｨｨ07, 0705ｨ - ｨｪｨｨ080609ｨ ｨｪｨｨ07, 0708ｨｨｨｬ02ｨｪ02ｨｪｨｨ07 ｨｨ ｨｪｨｨ ｨｺｨｰｨｨ09ｨｪ0609ｨｰｨｨ ｨｮ ﾂ00ｨｰ06ｨｬ 05ｨｰｨｨ01 ｨ ｨｨ ｨ 02ｨｨｨｦ ｨ ｨｪ ｨｪ06ｨｬ 06ｨ ｨｰｨ ｨｪｨ 05ｨｨ03ｨｹ ｨｬｨ 05ｨ 07 ﾂｨ 09ｨｰｨｹ 0002 ｨｪ02 ｨｰｨｨ ﾂ02 09ｨｺｨｨ01 00ｨ ｨｺ ｨｰ ﾂ ｨｺｨ, 06ｨｺｨ ｨ 06 ｨｴｨｨ01 04ｨ ｨｬ02ｨｰ ｨｪ ｨｨ 07 ｨｪｨｨ02 ｨｪｨ ｨｪｨｨ ｨｪ02 ｨｪｨｨｨｦ 0708ｨｨ ｨｪｨｨｨｨ ｨｨ ｨｺ ｨｰｨｨ09 - ｨｪ0609ｨｰｨｨ. 0507ｨｨ0906ｨｺ 05ｨｨｨｰ0208ｨ ｨｰｨｮ Aki hi ko S., Step hen A. Spec tor Ef fect of Host Ge ne tic Va ri a - ti on on the Phar ma co ki ne tics and Cli ni cal Res pon se of Non-nuc le - o si de Re ver se Tran s c rip ta se In hi bi tors // Fu tur HIV Ther. ｪ ｪ Vol. 2, 011. ｪ P. 69 ｪ Alfirevic A., Pirmohamed M. Drug induced hypersensitivity and the HLA com p lex // Phar ma ce u ti cals. ｪ ｪ Vol. 4. ｪ P. 69 ｪ Anderson K.S. A transient kinetic approach to investigate nuc le o si de in hi bi tors of mi toc hon d ri al DNA po ly me ra se gam ma // Met hods. ｪ ｪ Vol. 51, 014. ｪ P. 392 ｪ An der son P.L., Lam ba J., Aqu i lan te C.L. et al. Phar ma co ge - netic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-in fec ted adults: a pi lot stu dy // J. Ac qu ir. Im mu ne De fic. Syndr. ｪ ｪ Vol. 42. ｪ P. 441 ｪ Ar ne do M., Taf fe P., Sah li R. et al. Con t ri bu ti on of 20 sin g le nuc le o ti de po ly mor p hisms of 13 ge nes to dys li pi de mia as so ci a ted with an ti ret ro vi ral the ra py // Phar ma co ge net. Ge no mics. ｪ ｪ Vol. 17, 019. ｪ P. 755 ｪ Asen si V., Re go C., Mon tes A.H., Col la zos J. et al. IL-1be ta (+3954C/T) polymorphism could protect human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral treat - ment (HAART) against lipodystrophic syndrome // Genet. Med. ｪ ｪ Vol. 10, 013. ｪ P. 215 ｪ Bi er man W.F., Schef fer G.L., Scho on der wo erd A. et al. Pro - tease inhibitors atazanavir, lopinavir and ritonavir are potent bloc - kers, but po or sub s t ra tes, of ABC tran s por ters in a bro ad pa nel of ABC tran s por ter-ove rex p res sing cell li nes // J. An ti mic rob. Che mot - her. ｪ ｪ Vol. 65, 018. ｪ P ｪ Bon net E., Ber nard J., Fa u vel J. et al. As so ci a ti on of APOC3 polymorphisms with both dyslipidemia and lipoatrophy in HA - ART-receiving patients // AIDS Res. Hum. Retroviruses. ｪ ｪ Vol. 24, 012. ｪ P. 169 ｪ Brown K.C., Hos se i ni po ur M.C., Hos kins J.M. Et al. Ex p lo - ra ti on of CYP450 and drug tran s por ter ge no ty pes and cor re la ti ons with ne vi ra pi ne ex po su re in Ma la wi ans // Phar ma co ge no mics. ｪ ｪ Vol. 13, 011. ｪ P. 113 ｪ Cas te lar L., Sil va M.M., Cas tel li E.C. et al. In ter le u kin-18 and in ter fe ron-gam ma po ly mor p hisms in Bra zi li an hu man im mu no - deficiency virus-1-infected patients presenting with lipodystrophy syn d ro me // Tis sue An ti gens. ｪ ｪ Vol. 76, 012. ｪ P. 126 ｪ Chiappini F., Teicher E., Saffroy R. et al. Relationship bet - we en po ly me ra se gam ma (POLG) po ly mor p hisms and an ti ret ro vi ral the ra py-in du ced li po dys t rop hy in HIV-1 in fec ted pa ti ents: a ca - se-con t rol stu dy // Curr. HIV Res. ｪ ｪ Vol. 7, 012. ｪ P. 244 ｪ Fos ter S.B., Lu M., Thom p son B., Rich K.C., Ma tu - kas L.M., Ma son R., Win c hes ter R., Mac Do nald K.S., She a rer W.T. As so ci a ti on bet we en HLA in he ri tan ce and as t h ma me di ca ti on use in HIV po si ti ve chil d ren // Aids. ｪ ｪ Vol. 24, ｪ P ｪ He il S.G., van der En de M.E., Schenk P.W. et al. As so ci a ti - ons bet we en ABCB1, CYP2A6, CYP2B6, CYP2D6, and CYP3A5 alleles in relation to efavirenz and nevirapine pharmacokinetics in HIV-in fec ted in di vi du als // Ther. Drug Mo nit. ｪ ｪ Vol. 34, 012. ｪ P. 153 ｪ Hu ang X., Ling H., Mao W., Ding X. et al. Hu man le u ko cy - te antigen profile in HIV-1 infected individuals and AIDS patients from Chon g qing, Chi na // Mic ro bi ol. Im mu nol. ｪ ｪ Vol. 53, 019. ｪ P. 512 ｪ Kal li an pur A.R., Hul gan T., Can ter J.A. et al. He moc h ro - ma to sis (HFE) ge ne mu ta ti ons and pe rip he ral ne u ro pat hy du ring an ti ret ro vi ral the ra py // AIDS. ｪ ｪ Vol. 20. ｪ P ｪ

5 ｪ ｪ Kal li an pur A.R., Hul gan T. Phar ma co ge ne tics of nuc le o si de re ver se-tran s c rip ta se in hi bi tor-as so ci a ted pe rip he ral ne u ro pat hy // Phar ma co ge no mics. ｪ ｪ Vol. 10. ｪ P. 623 ｪ Kir by B.J., Col li er A.C., Kha rasch E.D. et al. Com p lex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ri to na vir or ne lfi na vir // Drug Me tab. Dis pos. ｪ ｪ Vol. 39, ｪ P ｪ Mal lal S., Phil lips E., Ca ro si G. et al. HLA-B*5701 scre e - ning for hy per sen si ti vi ty to aba ca vir // N. Engl. J. Med. ｪ ｪ Vol. 358, 016. ｪ P. 568 ｪ Mar zoc chet ti A., Schwarz J., Di Gi am be ne det to S. et al. The ef fect of po ly mor p hisms in can di da te ge nes on the long-term risk of lipodystrophy and dyslipidemia in HIV-infected white patients star - ting an ti ret ro vi ral the ra py // AIDS Res. Hum. Ret ro vi ru ses. ｪ ｪ Vol. 27, ｪ P ｪ Ma se be T.M., Bes song P.O., Nwo be ga hay J. et al. Pre va len - ce of MDR1 C3435T and CYP2B6 G516T po ly mor p hisms among HIV-1 in fec ted So uth Af ri can pa ti ents // Dis. Mar kers. ｪ ｪ Vol. 32, 011. ｪ P. 43 ｪ No lan D., Mo o re C., Cas t ley A. et al. Tu mo ur ne cro sis fac tor-1 7 gene-238g/a promoter polymorphism associated with a more rapid onset of li po dys t rop hy // AIDS. ｪ ｪ Vol. 17. ｪ P. 121 ｪ Rizzardini G, Zucchi P. Abacavir and lamivudine for the tre - at ment of hu man im mu no de fi ci en cy vi rus // Ex pert. Opin. Phar ma - cot her. ｪ ｪ Vol. 12, ｪ P ｪ San c hez H.V., Gu ti er rez R.F. To xi co ge ne tics of an ti ret ro - vi ral tre at ment (II): ne u ro to xi ci ty, he pa to to xi ci ty, lac tic aci do sis, kid ney da ma ge, and ot her ad ver se ef fects of an ti ret ro vi ral drugs // En ferm. In fecc. Mic ro bi ol. Clin. ｪ ｪ Vol. 26, 016. ｪ P. 24 ｪ Sil va M.M., Si mo es R.T., Cas tel li E.C. et al. TNF mic ro sa - tel li te al le les may con fer pro tec ti on aga inst the de ve lop ment of li po - dys t rop hy syn d ro me in Bra zi li an HIV pa ti ents // Int. J. Im mu no ge - net. ｪ ｪ Vol. 37, 015. ｪ P. 379 ｪ Tarr P.E., Telenti A. Toxicogenetics of antiretroviral therapy: genetic factors that contribute to metabolic complications // Antivir. Ther. ｪ ｪ Vol. 12, 017. ｪ P. 999 ｪ Tozzi V. Pharmacogenetics of antiretrovirals // Antiviral Res. ｪ ｪ Vol. 85, 011. ｪ P. 190 ｪ Wang L., McLe od H.L. et al. Ge no mics and Drug Res pon se // N. Engl. J. Med. ｪ ｪ Vol ｪ P ｪ Za no ne P.B., Ri va A., Na si M. et al. Ge ne tic po ly mor p hisms dif fe ren t ly in f lu en cing the emer gen ce of at rop hy and fat ac cu mu la ti - on in HIV-re la ted li po dys t rop hy // AIDS. ｪ ｪ Vol. 22, ｪ P ｪ1778. The in flu ence of hu man ge netic fac tors on HAART Tumanov A.S. The D.I. Ivanovsky In sti tute of Vi rol ogy of The Min is try of Health of The Rus sian Fed er a tion; , Rus sia, Mos cow, Gamaleya str., 16; fax/phone: , desep@mail.ru The re view dis cusses role of hu man ge netic fac tors in ef fi ciency and com pli ca tions of highly ac tive antiretrovirus ther apy (HAART). Ge netic poly mor phism of cytochrom P450 and multidrug re sis tance sys tems (spe cif i cally, CYP2B6 and MDR1/MRP1/P-gp, re spec - tively) af fects intracellular con cen tra tion of nu mer ous antiretroviral drugs (AD) that may ex plain dif fer ences in clin i cal ef fi cacy of HAART. Ge netic back ground might also im pact in rate of mis cel la neous com pli ca tions in pa tients re ceiv ing HAART. Thus hy per sen si - tiv ity to re verse tran scrip tase in hib i tors has been shown to be de pend ent on the pres ence of TNF al pha cytokine gene vari ant 308A or some al leles of HLA class I (HLA-B*5701, HLA-B*3505, HLA-B*14, HLA-Cw*4, HLA-Cw*8) or class II (HLA-DRB1*0101) loci. Pro tec - tion from lipodistrophia that rep re sents se ri ous com pli ca tion of HAART de pends on pres ence of par tic u lar al leles of poly mor phic cytokine genes IL-1, IL-18 and TNF beta. Vice versa, sus cep ti bil ity to en hanced trigleciride level fol low ing HAART is as so ci ated with polymorphic alleles of APOC3, ARb2, ARb3, HFE, LPIN1 and POLG loci whereas in creased risk of neu rop a thy is as so ci ated with ge - netic vari ants G516T and C983T of CYP2B6 gene. Var i ous com pli ca tions like hyperbilirubinemia,neutropenia and astma were found to be as so ci ated with UGT1A1*28 that con trols small lipophilic mol e cules, A1203A (rs ) of MRP4 and HLA-A*68, respectively. Data clearly dem on strates the need in per son al iza tion through ge netic pro fil ing in HAART to in crease its ef fi ciency and de crease the rate of complications. Key words: HIV-1, hu man ge netic fac tors, Highly Ac tive Antiretroviral Ther apy (HAART) ISSN