Pharmacogenetics of Thiopurine Drugs: Role of Thiopurine S-Methyltransferase and Nucleoside Diphosphate-Linked Moiety X Motif 15 Genetic Polymorphisms on Drugs-induced Myelosuppression

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Kanyarat Khaeso
Nontaya Nakkam
Sirimas Kanjanawart
Suda Vannaprasaht
Patcharee Komvilaisak
Wichittra Tassaneeyakul

Abstract

ยากลุ่ม thiopurines ได้แก่ 6-mercaptopurine (6-MP), 6-thioguanine (6-TG) และ azathioprine (AZA) เป็นยาที่ใช้อย่างแพร่หลายในการรักษาโรคมะเร็ง เช่น มะเร็งเม็ดเลือดขาวเฉียบพลันชนิดลิมโฟบลาสติก มะเร็งเม็ดเลือดขาวเรื้อรังชนิดมัยอีลอยด์ มะเร็งเม็ดเลือดขาวเฉียบพลันชนิดมัยอีลอยด์ มะเร็งต่อมน้ำเหลือง รวมไปถึงใช้ในการรักษาโรคภูมิต้านเนื้อเยื่อของตนเองและโรคที่เกิดจากการอักเสบ อย่างไรก็ตาม เป็นที่ทราบกันดีว่ายาในกลุ่มนี้ทำให้เกิดพิษรุนแรง โดยเฉพาะอย่างยิ่งภาวะกดไขกระดูก ปัจจุบัน มีรายงานว่าความหลากหลายทางพันธุกรรมของยีน thiopurine S-methyltransferase (TPMT) และ nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) มีความสัมพันธ์อย่างมากกับการเกิดภาวะกดไขกระดูกของยากลุ่มนี้ ซึ่ง TPMT และ NUDT15 เป็นเอนไซม์หลักที่เกี่ยวข้องในกระบวนการเมแทบอลิซึม ของยา thiopurines  บทความนี้เป็นการทบทวนวรรณกรรมเกี่ยวกับความหลากหลายทางพันธุกรรมของเอนไซม์เหล่านี้ และความสัมพันธ์กับการเกิดภาวะกดไขกระดูกของยากลุ่ม thiopurines โดยเน้นถึงความแตกต่างกันในประชากรแต่ละเชื้อชาติ

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