Histamine H2 Receptor Polymorphisms, Myocardial Transcripts, and Heart Failure (from the Multi-Ethnic Study of Atherosclerosis and Beta-Blocker Effect on Remodeling and Gene Expression Trial)

Peter J. Leary, Richard A. Kronmal, David A. Bluemke, Peter M. Buttrick, Kenneth L. Jones, David P. Kao, Steven M. Kawut, Eric V. Krieger, Joao Lima, Wayne Minobe, David D. Ralph, Ryan J. Tedford, Noel S. Weiss, Michael R. Bristow

Research output: Contribution to journalArticle

Abstract

Myocardial H2 receptor activation contributes to heart failure (HF) in preclinical models, and H2 receptor antagonists are associated with decreased HF incidence. This study evaluated whether H2 histamine receptor (HRH2) single nucleotide polymorphisms (SNPs) are associated with HF incidence and whether myocardial transcript abundance is associated with HF recovery. The association of SNPs in HRH2 with incident HF was characterized using Cox proportional hazards regression among participants in the Multi-Ethnic Study of Atherosclerosis. Differences in myocardial HRH2 transcripts were characterized in participants with dilated cardiomyopathy comparing 6 "super-responders" with 6 nonresponders to β blockade in the Beta-Blocker Effect on Remodeling and Gene Expression Trial. In MESA, no candidate SNP was associated with HF in black, Hispanic, or white participants. The rs2241562 minor allele was present only in Chinese participants and the adjusted HF hazard among those with 1 or more copies of this allele was 3.7, 95% confidence interval 1.0 to 13.4. In BORG, super-responders to β blockade had higher levels of myocardial HRH2 transcript at baseline compared with nonresponders (fragments per kilobase per transcript per million mapped reads: Variant 2, 5.5 ± 1.1 compared with 3.2 ± 0.8 in nonresponders, p = 0.002; Variant 1 + 2, 32.1 ± 7.4 compared with 23.3 ± 4.2 in nonresponders, p = 0.04). In conclusion, the presence of a minor allele at rs2241562 was associated with increased HF incidence in Chinese participants. Differences in myocardial HRH2 transcript abundance were seen in participants with dilated cardiomyopathy who responded to β blockade. These observations support the hypothesis that HRH2 is involved in the pathogenesis of HF.

Original languageEnglish (US)
JournalAmerican Journal of Cardiology
DOIs
StateAccepted/In press - Jan 1 2017

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Histamine H2 Receptors
Atherosclerosis
Heart Failure
Gene Expression
Single Nucleotide Polymorphism
Alleles
Dilated Cardiomyopathy
Incidence
Hispanic Americans
Confidence Intervals

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Histamine H2 Receptor Polymorphisms, Myocardial Transcripts, and Heart Failure (from the Multi-Ethnic Study of Atherosclerosis and Beta-Blocker Effect on Remodeling and Gene Expression Trial). / Leary, Peter J.; Kronmal, Richard A.; Bluemke, David A.; Buttrick, Peter M.; Jones, Kenneth L.; Kao, David P.; Kawut, Steven M.; Krieger, Eric V.; Lima, Joao; Minobe, Wayne; Ralph, David D.; Tedford, Ryan J.; Weiss, Noel S.; Bristow, Michael R.

In: American Journal of Cardiology, 01.01.2017.

Research output: Contribution to journalArticle

Leary, Peter J. ; Kronmal, Richard A. ; Bluemke, David A. ; Buttrick, Peter M. ; Jones, Kenneth L. ; Kao, David P. ; Kawut, Steven M. ; Krieger, Eric V. ; Lima, Joao ; Minobe, Wayne ; Ralph, David D. ; Tedford, Ryan J. ; Weiss, Noel S. ; Bristow, Michael R. / Histamine H2 Receptor Polymorphisms, Myocardial Transcripts, and Heart Failure (from the Multi-Ethnic Study of Atherosclerosis and Beta-Blocker Effect on Remodeling and Gene Expression Trial). In: American Journal of Cardiology. 2017.
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abstract = "Myocardial H2 receptor activation contributes to heart failure (HF) in preclinical models, and H2 receptor antagonists are associated with decreased HF incidence. This study evaluated whether H2 histamine receptor (HRH2) single nucleotide polymorphisms (SNPs) are associated with HF incidence and whether myocardial transcript abundance is associated with HF recovery. The association of SNPs in HRH2 with incident HF was characterized using Cox proportional hazards regression among participants in the Multi-Ethnic Study of Atherosclerosis. Differences in myocardial HRH2 transcripts were characterized in participants with dilated cardiomyopathy comparing 6 {"}super-responders{"} with 6 nonresponders to β blockade in the Beta-Blocker Effect on Remodeling and Gene Expression Trial. In MESA, no candidate SNP was associated with HF in black, Hispanic, or white participants. The rs2241562 minor allele was present only in Chinese participants and the adjusted HF hazard among those with 1 or more copies of this allele was 3.7, 95{\%} confidence interval 1.0 to 13.4. In BORG, super-responders to β blockade had higher levels of myocardial HRH2 transcript at baseline compared with nonresponders (fragments per kilobase per transcript per million mapped reads: Variant 2, 5.5 ± 1.1 compared with 3.2 ± 0.8 in nonresponders, p = 0.002; Variant 1 + 2, 32.1 ± 7.4 compared with 23.3 ± 4.2 in nonresponders, p = 0.04). In conclusion, the presence of a minor allele at rs2241562 was associated with increased HF incidence in Chinese participants. Differences in myocardial HRH2 transcript abundance were seen in participants with dilated cardiomyopathy who responded to β blockade. These observations support the hypothesis that HRH2 is involved in the pathogenesis of HF.",
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AU - Jones, Kenneth L.

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