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. 2018 Jan 15;121(2):256-261.
doi: 10.1016/j.amjcard.2017.10.016. Epub 2017 Oct 20.

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  1 , Richard A Kronmal  2 , David A Bluemke  3 , Peter M Buttrick  4 , Kenneth L Jones  4 , David P Kao  4 , Steven M Kawut  5 , Eric V Krieger  6 , Joao A Lima  7 , Wayne Minobe  4 , David D Ralph  6 , Ryan J Tedford  8 , Noel S Weiss  9 , Michael R Bristow  4
Affiliations

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 et al. Am J Cardiol. .

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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Conflict of interest statement

Disclosures: No author reported a conflict of interest related to this work.

Figures

Figure 1
Figure 1
Study Sample. Flow diagram characterizing MESA participants who contributed the analysis cohorts.
Figure 2
Figure 2
Study Sample. Flow diagram characterizing BORG participants who contributed the analysis cohort.
See this image and copyright information in PMC

References

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    1. Kao DP, Lowes BD, Gilbert EM, Minobe W, Epperson LE, Meyer LK, Ferguson DA, Volkman AK, Zolty R, Borg CD, Quaife RA, Bristow MR. Therapeutic Molecular Phenotype of β-Blocker-Associated Reverse-Remodeling in Nonischemic Dilated Cardiomyopathy. Circ Cardiovasc Gen. 2015;8:270–283. - PMC - PubMed
    1. MESA Manual of Operations: Field Center and Laboratory Procedures. mesa-nhlbiorg. Available at: http://www.mesa-nhlbi.org/manuals.aspx. Accessed March 17, 2014.

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