Impact of four loci on serum tamsulosin hydrochloride concentration

Ryo Takata, Koichi Matsuda, Jun Sugimura, Wataru Obara, Tomoaki Fujioka, Koji Okihara, Natsuki Takaha, Tsuneharu Miki, Shingo Ashida, Keiji Inoue, Chizu Tanikawa, Taro Shuin, Shoichi Sasaki, Yoshiyuki Kojima, Kenjiro Kohri, Michiaki Kubo, Masao Yamaguchi, Yozo Ohnishi, Yusuke Nakamura

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)21-26
Number of pages6
JournalJournal of Human Genetics
Volume58
Issue number1
DOIs
Publication statusPublished - 01-01-2013

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tamsulosin
Serum
Prostatic Hyperplasia
Single Nucleotide Polymorphism
Pharmacokinetics
Genome-Wide Association Study

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Takata, R., Matsuda, K., Sugimura, J., Obara, W., Fujioka, T., Okihara, K., ... Nakamura, Y. (2013). Impact of four loci on serum tamsulosin hydrochloride concentration. Journal of Human Genetics, 58(1), 21-26. https://doi.org/10.1038/jhg.2012.126
Takata, Ryo ; Matsuda, Koichi ; Sugimura, Jun ; Obara, Wataru ; Fujioka, Tomoaki ; Okihara, Koji ; Takaha, Natsuki ; Miki, Tsuneharu ; Ashida, Shingo ; Inoue, Keiji ; Tanikawa, Chizu ; Shuin, Taro ; Sasaki, Shoichi ; Kojima, Yoshiyuki ; Kohri, Kenjiro ; Kubo, Michiaki ; Yamaguchi, Masao ; Ohnishi, Yozo ; Nakamura, Yusuke. / Impact of four loci on serum tamsulosin hydrochloride concentration. In: Journal of Human Genetics. 2013 ; Vol. 58, No. 1. pp. 21-26.
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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.",
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Takata, R, Matsuda, K, Sugimura, J, Obara, W, Fujioka, T, Okihara, K, Takaha, N, Miki, T, Ashida, S, Inoue, K, Tanikawa, C, Shuin, T, Sasaki, S, Kojima, Y, Kohri, K, Kubo, M, Yamaguchi, M, Ohnishi, Y & Nakamura, Y 2013, 'Impact of four loci on serum tamsulosin hydrochloride concentration', Journal of Human Genetics, vol. 58, no. 1, pp. 21-26. https://doi.org/10.1038/jhg.2012.126

Impact of four loci on serum tamsulosin hydrochloride concentration. / Takata, Ryo; Matsuda, Koichi; Sugimura, Jun; Obara, Wataru; Fujioka, Tomoaki; Okihara, Koji; Takaha, Natsuki; Miki, Tsuneharu; Ashida, Shingo; Inoue, Keiji; Tanikawa, Chizu; Shuin, Taro; Sasaki, Shoichi; Kojima, Yoshiyuki; Kohri, Kenjiro; Kubo, Michiaki; Yamaguchi, Masao; Ohnishi, Yozo; Nakamura, Yusuke.

In: Journal of Human Genetics, Vol. 58, No. 1, 01.01.2013, p. 21-26.

Research output: Contribution to journalArticle

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T1 - Impact of four loci on serum tamsulosin hydrochloride concentration

AU - Takata, Ryo

AU - Matsuda, Koichi

AU - Sugimura, Jun

AU - Obara, Wataru

AU - Fujioka, Tomoaki

AU - Okihara, Koji

AU - Takaha, Natsuki

AU - Miki, Tsuneharu

AU - Ashida, Shingo

AU - Inoue, Keiji

AU - Tanikawa, Chizu

AU - Shuin, Taro

AU - Sasaki, Shoichi

AU - Kojima, Yoshiyuki

AU - Kohri, Kenjiro

AU - Kubo, Michiaki

AU - Yamaguchi, Masao

AU - Ohnishi, Yozo

AU - Nakamura, Yusuke

PY - 2013/1/1

Y1 - 2013/1/1

N2 - 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.

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Takata R, Matsuda K, Sugimura J, Obara W, Fujioka T, Okihara K et al. Impact of four loci on serum tamsulosin hydrochloride concentration. Journal of Human Genetics. 2013 Jan 1;58(1):21-26. https://doi.org/10.1038/jhg.2012.126