The pK56M ICAM1 HFpEF risk variant and inflammatory biomarkers

Pedro Giro; Kent D. Taylor; Sanjiv J. Shah; Ravi B. Patel

doi:10.1016/j.ahjo.2023.100346

The pK56M ICAM1 HFpEF risk variant and inflammatory biomarkers

Pedro Giro, Kent D. Taylor, Sanjiv J. Shah, Ravi B. Patel^*

^*Corresponding author for this work

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Introduction: The ICAM1 variant rs5491 (p.K56M) is common among Black individuals and has been associated with risk of heart failure with preserved ejection fraction (HFpEF). The pathways by which rs5491 leads to HFpEF are not known. Methods: Among Black individuals within the Multi-Ethnic Study of Atherosclerosis, we evaluated associations of rs5491 with 3 inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α receptor 1 [TNFR-1]). Results: Among 1558 Black participants (mean age 62 ± 10 y, 47 % female), each additional rs5491 allele was associated with higher hsCRP after covariate adjustment (β: 0.15, SE: 0.07, P = 0.02). Each additional rs5491 allele was associated with higher TNFR-1 (β: 0.06, SE: 0.02, P = 0.02), but not IL-6 (β: 0.04, SE: 0.04, P = 0.29). The association between rs5491 and HFpEF remained significant after adjustment for hsCRP. Conclusion: In Black individuals, rs5491 (p.K56M) is associated with higher hsCRP and higher TNFR-1, but not IL-6.

Original language	English (US)
Article number	100346
Journal	American Heart Journal Plus: Cardiology Research and Practice
Volume	36
DOIs	https://doi.org/10.1016/j.ahjo.2023.100346
State	Published - Dec 2023

Funding

This work was supported by grants KL2TR001424 from the National Center for Advancing Translational Sciences , U.S. National Institutes of Health (NIH). MESA and the MESA SHARe project are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1-TR-001881, and DK063491. Funding for SHARe genotyping was provided by NHLBI Contract N02-HL-64278 . Genotyping was performed at Affymetrix (Santa Clara, California, USA) and the Broad Institute of Harvard and MIT (Boston, Massachusetts, USA) using the Affymetrix Genome-Wide Human SNP Array 6.0.

Keywords

Heart failure with preserved ejection fraction
ICAM-1
hsCRP

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.ahjo.2023.100346

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@article{a5ee019003094641935410491d2c3dba,

title = "The pK56M ICAM1 HFpEF risk variant and inflammatory biomarkers",

abstract = "Introduction: The ICAM1 variant rs5491 (p.K56M) is common among Black individuals and has been associated with risk of heart failure with preserved ejection fraction (HFpEF). The pathways by which rs5491 leads to HFpEF are not known. Methods: Among Black individuals within the Multi-Ethnic Study of Atherosclerosis, we evaluated associations of rs5491 with 3 inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α receptor 1 [TNFR-1]). Results: Among 1558 Black participants (mean age 62 ± 10 y, 47 % female), each additional rs5491 allele was associated with higher hsCRP after covariate adjustment (β: 0.15, SE: 0.07, P = 0.02). Each additional rs5491 allele was associated with higher TNFR-1 (β: 0.06, SE: 0.02, P = 0.02), but not IL-6 (β: 0.04, SE: 0.04, P = 0.29). The association between rs5491 and HFpEF remained significant after adjustment for hsCRP. Conclusion: In Black individuals, rs5491 (p.K56M) is associated with higher hsCRP and higher TNFR-1, but not IL-6.",

keywords = "Heart failure with preserved ejection fraction, ICAM-1, hsCRP",

author = "Pedro Giro and Taylor, {Kent D.} and Shah, {Sanjiv J.} and Patel, {Ravi B.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = dec,

doi = "10.1016/j.ahjo.2023.100346",

language = "English (US)",

volume = "36",

journal = "American Heart Journal Plus: Cardiology Research and Practice",

issn = "2666-6022",

publisher = "Elsevier Inc.",

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T1 - The pK56M ICAM1 HFpEF risk variant and inflammatory biomarkers

AU - Giro, Pedro

AU - Taylor, Kent D.

AU - Shah, Sanjiv J.

AU - Patel, Ravi B.

PY - 2023/12

Y1 - 2023/12

N2 - Introduction: The ICAM1 variant rs5491 (p.K56M) is common among Black individuals and has been associated with risk of heart failure with preserved ejection fraction (HFpEF). The pathways by which rs5491 leads to HFpEF are not known. Methods: Among Black individuals within the Multi-Ethnic Study of Atherosclerosis, we evaluated associations of rs5491 with 3 inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α receptor 1 [TNFR-1]). Results: Among 1558 Black participants (mean age 62 ± 10 y, 47 % female), each additional rs5491 allele was associated with higher hsCRP after covariate adjustment (β: 0.15, SE: 0.07, P = 0.02). Each additional rs5491 allele was associated with higher TNFR-1 (β: 0.06, SE: 0.02, P = 0.02), but not IL-6 (β: 0.04, SE: 0.04, P = 0.29). The association between rs5491 and HFpEF remained significant after adjustment for hsCRP. Conclusion: In Black individuals, rs5491 (p.K56M) is associated with higher hsCRP and higher TNFR-1, but not IL-6.

AB - Introduction: The ICAM1 variant rs5491 (p.K56M) is common among Black individuals and has been associated with risk of heart failure with preserved ejection fraction (HFpEF). The pathways by which rs5491 leads to HFpEF are not known. Methods: Among Black individuals within the Multi-Ethnic Study of Atherosclerosis, we evaluated associations of rs5491 with 3 inflammatory biomarkers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 [IL-6], and tumor necrosis factor-α receptor 1 [TNFR-1]). Results: Among 1558 Black participants (mean age 62 ± 10 y, 47 % female), each additional rs5491 allele was associated with higher hsCRP after covariate adjustment (β: 0.15, SE: 0.07, P = 0.02). Each additional rs5491 allele was associated with higher TNFR-1 (β: 0.06, SE: 0.02, P = 0.02), but not IL-6 (β: 0.04, SE: 0.04, P = 0.29). The association between rs5491 and HFpEF remained significant after adjustment for hsCRP. Conclusion: In Black individuals, rs5491 (p.K56M) is associated with higher hsCRP and higher TNFR-1, but not IL-6.

KW - Heart failure with preserved ejection fraction

KW - ICAM-1

KW - hsCRP

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The pK56M ICAM1 HFpEF risk variant and inflammatory biomarkers

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