title: NUDT15 genotype distributions in the Korean population.
abstract: Thiopurines have a narrow therapeutic range because of frequent toxicity (i.e. marrow suppression), which is only partly explained by TPMT genetic polymorphisms, especially within Asian populations. Recent studies have identified NUDT15 variation as another important factor affecting thiopurine metabolism. In this study, a total of four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal) were genotyped in 920 Korean individuals using direct sequencing of NUDT15 for the first time in a Korean population. The allele frequencies were 86.7% for NUDT15*1, and 4.4, 6.9, 0.4, 1.1, and 0.50% for *2, *3, *4, *5, and *6, respectively. The NUDT15 phenotypes based on diplotypes included normal activity (n=692), intermediate activity (n=209), and low activity (n=19), occurring in 75.2, 22.7, and 2.1% of the population, respectively. This study was the first to report NUDT15 variants other than NUDT15*3 in the Korean population and more individuals who were categorized as having intermediate or low NUDT15 activity in our study than in previously reported studies in the Korean population (24.8 vs. 19.4%, P<0.05). This study is useful for future clinical studies on thiopurine pharmacogenetics and dosage adjustment in the Korean population.
authors.affiliation: Departments of aLaboratory Medicine and Genetics bPediatrics cInternal Medicine dClinical Pharmacology and Therapeutics eSamsung Advanced Institute for Health Sciences and Technology (SAIHST), Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyoung-Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Rihwa
authors.initials: R
authors.lastname: Choi
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Won
authors.forename: Yon Ho
authors.initials: YH
authors.lastname: Choe
authors.forename: Ben
authors.initials: B
authors.lastname: Kang
authors.forename: Kiwuk
authors.initials: K
authors.lastname: Lee
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Soo-Youn
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071184:Pharmacogenomic Variants; D011755:Pyrophosphatases / Q000235:genetics* / Q000378:metabolism*; D056910:Republic of Korea; D055815:Young Adult; D000096964:Nudix Hydrolases
chemical_list: D011755:Pyrophosphatases; C543721:NUDT15 protein, human; D000096964:Nudix Hydrolases