TY - JOUR
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
Y1 - 2013/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84873041932&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873041932&partnerID=8YFLogxK
U2 - 10.1038/jhg.2012.126
DO - 10.1038/jhg.2012.126
M3 - Article
C2 - 23151678
AN - SCOPUS:84873041932
SN - 1434-5161
VL - 58
SP - 21
EP - 26
JO - Journal of Human Genetics
JF - Journal of Human Genetics
IS - 1
ER -