Ethnic Variation in CYP2E1， GSTM1， GSTT1 Genes Polymorphism Analysis: Taiwan Aborigines,Thai and Filipino
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(2) 182. (drug metabolizing enzyme GSTT1. genetic polymorphism) (MDS). [27]. GSTT1 N-acetyl-transferase (NAT2). (slow. [26]. [28]. 50%. phenotype) 35%. 14% [4]. 5 P450 CYP. P450). N-nitrosamines. butadiene. 64.7. 13. [5]. c2/c2. 15. c1/c1. [6]. 14.6. 1:1 %. CY P 2 E 1. 10. 13.4. (cytochrome. 13.8. c2. c1. CYP2E1. N-nitrosamine CYP2E1. [7-10] [11-13]. [14]. [15]. CYP2E1. (heparin 5'. Pst I / Rsa I. 2. 10 c.c. c1. 3. EDTA). c1/c1. 4. c2. 48. c1/c2. RsaI. DNA. c2/c2 (RFLP) CYP2E1. 360bp. 50bp. 410bp 360bp. c1/c1. c2/c2. 410bp. CYP2E1. (PCR). 50bp. (heterozygous). Hayashi [6]. 5'- CCA GTC GAG TCT ACA TTC TCA-. c1/c2. [16]. 3'. (glutathione. 3'. 5'-TTC ATT CTG TCT TCT AAC TGGRsaI. (RFLP). GST). S-transferase. 6. 360bp. GSTM1 GST-. GSTT1. 410bp 360bp. GST-. 50bp c2/c2 50bp. GSTT1. 410bp c1/c2. [16]. GSTM1. Comstock [28]. GSTM1. c1/c1. Pemble [31] PCR. (null genotype)[17]. [14]. GSTT1. GSTM1. ATC TC-3' [18-26] GSTT1. GSTM1. GSTT1. 5'-TTC CTT ACT GGT CCT CAC CAG CA-3'. 5'-TCA CCG GAT CAT GGC GSTM1. CTG CCC TAC TTG ATT GAT GGG-3'. 5'5'-.
(3) 183. M. 1. 2. 3. 4. 1 CYP2E1-RsaI 1 4. 2 GSTM1. M 100bp 2 c1/c1. c1/c2. 1 2 3 4 5 6 7. GSTT1. c2/c2. 273 bp. -globin. 6 : GSTT1(+) GSTT1( ) CTG GAT TGT AGC AGA TCA TGC-3' -globin. GSTT1. 480 bp GSTM1. 3. 5'-ACA CAA. : 100 bp. GSTM1 (+). GSTM1(+). (+) GSTM1( ). 4. 3. 1. 2. 5. 7. GSTT1. GSTT1( ). GSTM1. ( ). 5'-CAA CTT. CTG TGT TCA CTA GC-3' CAT CCA CGT TCA CC-3' 60. GSTT1. GSTM1. 480bp. 273bp (non-null genotype). (null genotype). c2. -globin (p <0.05). PCR. (p <0.05) positive control. 100bp. (p <0.05) c2. -globin (p <0.05) dBASE III puls. SAS. (chi-square test) 2. GSTM1. GSTT1. PCR. GSTM1. (null. genotype) 52.1% 42.5% 1. CYP2E1. PCR-RFLP. 52.9%. 53.7%. 53.1%. 45.9% 67.9% (. 56% 2). c2 19.4% 36% 13.6%. 43.4% 22% 16%(. 29.6% 19.6%. 1). CYP2E1. GSTM1 (p < 0.05).
(4) 184. 1 CYP2E1-RsaI. p. *. c1/c1. c1/c2. c2/c2. c2. 103. 70 (67.9). 26 (25.2). 7. (6.80). 19.4. 38. 13 (34.2). 17 (44.7). 8. (21.1)*. 43.4*. 52. 26 (50.0). 21 (40.4). 5. (9.60). 29.6. 38. 19 (50.0). 11 (28.9). 8. (21.0)*. 36.0. 37. 22 (59.5). 14 (37.8). 1. (2.7). 22.0. 119. 87 (73.1). 26 (21.8). 6. (5.1). 16.0. 106. 81 (76.4). 21 (19.8). 4. (3.8). 13.6. 56. 36 (64.3). 18 (32.1). 2. (3.6). 19.6. 0.05. 2 GSTM1. GSTT1 GSTM1. *. (65.3). 42 (34.7). 26. (48.1). 28 (51.9). 37. (75.5). 12 (24.5)*. (42.5). 24. (60.0). 16 (40.0). (45.9). 22. (59.5). 15 (40.5)*. 105. (72.6). 32 (23.4). (52.9). 61. (58.7). 49 (41.3). (56.0). 28. (56.0). 22 (44.0). 63. (52.1). 79. (46.3). 29. (53.7). (46.9). 26. (53.1). 17 17 93. (67.9). (47.9). 121. 58. 54. 25. 49. 23. 40. 23. (57.5). 37. 20. (54.1). 137. 44. (32.1). 104. 49. (47.1). 55. 50. 22. (44.0). 28. p. GSTT1. 0.05. 3 GSTM1. GSTT1 GSTM1. GSTT1. 121. 38. (31.4). 20. (16.5). 41. (33.9). 22 (18.2). 54. 7. (12.9). 17. (31.5). 19. (35.2). 11. (20.4). 49. 17. (34.7). 6. (12.2). 20. (40.8). 6. (12.3). 40. 15. (37.5). 8. (20.0). 9. (22.5). 8. (20.0). 37. 11. (29.7). 9. (24.3). 11. (29.7). 6. (16.2). 137. 32. (23.4). 12. (8.8). 73. (53.3). 20 (14.6)*. 104. 28. (26.9). 21. (20.2). 33. (31.7). 22 (21.2). 50. 12. (24.0). 10. (20.0). 16. (32.0). 12 (24.0). GSTM1. GSTT1. GSTM1. GSTT1. GSTM1. GSTT1 p. 0.05. GSTM1. GSTT1.
(5) 185. GSTT1 24.5% 44%. 21%. 34.7%. 51.9%. 40%. 40.5%. 23.4%. 41.3% (. 28% [11,14,32]. c2. 19.6% c2 2). (19%. 28%). c2 GSTT1. (p < 0.05). (p <0.05). c2 GSTT1 (p < 0.05). CYP2E1 GSTM1. 18.2%. 20.4%. 20%. 12.3%. 16.2%. 56% (45%. 24%. (42.5%. 14.6% (47%. 21.2%. 63%) [11,14,19] 53%). 51%) [19,34]. GSTM1 (p <0.05) GSTM1 (p < 0.05)(. 3) GSTT1. 53% 16% [21]. [14] 15%. 36% [27]. GSTT1. 44%. (53%) [14]. (Austronesian) [29] [30]. [35]. 1971. 1980 1981. 1990. c2/c2 GSTM1 13 15. GSTM1 GSTM1 [19] (Hardy and Weinberg's law) CYP2E1 1%. c2. 6% [32-33] 19%. 28% [7,8]. 1% [32]. [35]. [18].
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(8) 188. Ethnic Variation in CYP2E1, GSTM1, GSTT1 Genes Polymorphism Analysis: Taiwan Aborigines, Thai and Filipino Chih-Mei Chen, Jan-Gowth Chang, Ying-Chin Ko1 Department of Medical Research, Division of Molecular Medicine, China Medical College Hospital, Taichung; and 1Department of Public Health, Kaoshiung Medical University, Kaoshiung, Taiwan, R.O.C.. Background. Individuals metabolize chemical substrates or drugs with different the susceptibility; the differences are especially noticeable among individuals who originate from different ethnic groups. Several studies have shown that the different susceptibilities could be determined using genetic polymorphisms of the enzymes which metabolized the substrate(s) or chemical(s). The polymorphisms of three genesCYP2E1, GSTM1, and GSTT1 have been linked to the susceptibilities of individuals to some cancers, In our study, we focussed on the differences of these three genes in Taiwan aborigines, Thai and Filipino populations. Method. The study population included members of various tribes of aboriginal people including the Pancah, Ayayal, Bunun, Paiwan, Puyumar, Min-nan, and natives of Thailand, and the Philippines. DNA was isolated from peripheral leukaocytes. The target DNA fragments were amplified using polymerase chain reaction, and genotype were determined using restriction fragment length polymorphism. Results. The frequency of c2 allele in members of the Pancah was 19.4%, of the Ayayal was 43.4%, of the Bununis was 29.6%, of the Paiwan was 36%, of the Puyumar was 22%, of the Min-nan was 19.6%, of the Thai was 16%, and of the Filipinos was 13.6%. The frequency of GSTM1 null genotype was 56% in members of the Min-nan, 63% of the Pancah, 53% of the Ayayal, 53% of the Bunun, 42.5% of the Paiwan, 46% of the Puyumar, 48% of the Thai, and 53% of the Filipinos. The GSTT1 null genotype frequency was 44% in the members of the Min-nan, 35% of the Pancah, 52% of the Ayayal, 25% of the Bunun, 40% of the Paiwan, 41% of the Puyumar, 23% of the Thai, and 41% of the Filipinos. Co n c l u s i o n s . The CYP2E1-RsaI polymorphisms vary among different ethnic groups. T h e frequency of GSTT1 null genotype in members of the Puyumar and Thai p o p u l a t i o n s we r e s i g n i f i c a n t l y l owe r t h a n t h a t o f t h e M i n - n a n . T h e G S T M 1 polymorphism was not significantly different among the populations in this study. ( Mid Taiwan J Med 2000;5:181-8). Key words CYP2E1, ethnic, GSTM1, GSTT1, polymorphism, Taiwan aborigines. Received : July 12, 2000.. Revised : July 21, 2000.. Accepted : July 25, 2000. Address reprint requests to : Ying-Chin Ko, Department of Public Health, Kaoshinng Medical Univevsity, No 100, Shih-Chuan 1st Road, Kaoshiung 807, Taiwan, R.O.C..
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