title: Impact of four loci on serum tamsulosin hydrochloride concentration.
abstract: Tamsulosin hydrochloride is one of the most potent drugs for treatment of benign prostatic hyperplasia (BPH), however, the efficacy of tamsulosin hydrochloride varies among individuals. In this study, we measured the maximum serum concentration (Cmax) of tamsulosin hydrochloride in 182 of BPH patients and found remarkable individual variability. To investigate the genetic factors that regulate pharmacokinetics of tamsulosin hydrochloride, we conducted a genome-wide association study in these 182 BPH patients. As a result, rs16902947 on chromosome 5p13.2, rs7779057 on 7q22.3, rs35681285 on 7p21.2 and rs2122469 on 8p21.3 indicated possible associations with Cmax of tamsulosin hydrochloride (P=1.29 × 10(-7), 2.15 × 10(-7), 4.35 × 10(-7) and 7.03 × 10(-7), respectively), although these single-nucleotide polymorphisms (SNPs) did not reach the genome-wide significance threshold after Bonferroni correction. As these associated SNPs showed additive effects on serum tamsulosin hydrochloride concentration, we defined the 'Cmax prediction index' based on genotypes of these SNPs. This index clearly associated with Cmax values (P=4.5 × 10(-6)), indicating the possible roles of these four variants in tamsulosin hydrochloride pharmacokinetics. Our findings would partially explain the variability of the response to the tamsulosin hydrochloride treatment.
authors.affiliation: Department of Urology, Iwate Medical University, Morioka, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Takata
authors.forename: Koichi
authors.initials: K
authors.lastname: Matsuda
authors.forename: Jun
authors.initials: J
authors.lastname: Sugimura
authors.forename: Wataru
authors.initials: W
authors.lastname: Obara
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Fujioka
authors.forename: Koji
authors.initials: K
authors.lastname: Okihara
authors.forename: Natsuki
authors.initials: N
authors.lastname: Takaha
authors.forename: Tsuneharu
authors.initials: T
authors.lastname: Miki
authors.forename: Shingo
authors.initials: S
authors.lastname: Ashida
authors.forename: Keiji
authors.initials: K
authors.lastname: Inoue
authors.forename: Chizu
authors.initials: C
authors.lastname: Tanikawa
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Masao
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Yozo
authors.initials: Y
authors.lastname: Ohnishi
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004334:Drug Administration Schedule; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000235:genetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077409:Tamsulosin
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D013449:Sulfonamides; D000077409:Tamsulosin