Genome-wide response to antihypertensive medication using home blood pressure measurements: a pilot study nested within the HOMED-BP study

Kei Kamide, Kei Asayama, Tomohiro Katsuya, Takayoshi Ohkubo, Takuo Hirose, Ryusuke Inoue, Hirohito Metoki, Masahiro Kikuya, Taku Obara, Hironori Hanada, Lutgarde Thijs, Tatiana Kuznetsova, Yuichi Noguchi, Ken Sugimoto, Mitsuru Ohishi, Shigeto Morimoto, Takeshi Nakahashi, Shin Takiuchi, Toshihiko Ishimitsu, Takuya TsuchihashiMasayoshi Soma, Jitsuo Higaki, Hideo Matsuura, Tatsuo Shinagawa, Toshiyuki Sasaguri, Tetsuro Miki, Kazuo Takeda, Kazuaki Shimamoto, Michio Ueno, Naohisa Hosomi, Jyouji Kato, Norio Komai, Shunichi Kojima, Kazuhiro Sase, Toshiyuki Miyata, Hitonobu Tomoike, Yuhei Kawano, Toshio Ogihara, Hiromi Rakugi, Jan A. Staessen, Yutaka Imai*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)

Abstract

Background: Patients with mild-to-moderate essential hypertension in the HOMED-BP trial were randomly allocated to first-line treatment with a calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Methods: We recruited 265 (93 for CCB, 71 for ACEI and 101 for ARB) patients who completed the genomic study. Home blood pressure was measured for 5 days off-treatment before randomization and for 5 days after 2-4 weeks of randomized drug treatment. Genotyping was performed by 500K DNA microarray chips. The blood pressure responses to the three drugs were analyzed separately as a quantitative trait. For replication of SNPs with p <10(-4), we used the multicenter GEANE study, in which patients were randomized to valsartan or amlodipine. Results: SNPs in PICALM, TANC2, NUMA1 and APCDD1 were found to be associated with CCB responses and those in ABCC9 and YIPF1 were found to be associated with ARB response with replication. Conclusion: Our approach, the first based on high-fidelity phenotyping by home blood pressure measurement, might be a step in moving towards the personalized treatment of hypertension. Original submitted 29 April 2013; Revision submitted 14 August 2013
Original languageEnglish
Pages (from-to)1709-1721
JournalPharmacogenomics
Volume14
Issue number14
DOIs
Publication statusPublished - Nov 2013

Keywords

  • antihypertensive drugs
  • blood pressure response
  • n genome wide association study
  • home blood pressure
  • personalized treatment

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