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Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan.

Publication ,  Journal Article
Durda, P; Sabourin, J; Lange, EM; Nalls, MA; Mychaleckyj, JC; Jenny, NS; Li, J; Walston, J; Harris, TB; Psaty, BM; Valdar, W; Liu, Y ...
Published in: Arterioscler Thromb Vasc Biol
October 2015

OBJECTIVE: Interleukin (IL) -2 receptor subunit α regulates lymphocyte activation, which plays an important role in atherosclerosis. Associations between soluble IL-2Rα (sIL-2Rα) and cardiovascular disease (CVD) have not been widely studied and little is known about the genetic determinants of sIL-2Rα levels. APPROACH AND RESULTS: We measured baseline levels of sIL-2Rα in 4408 European American (EA) and 766 African American (AA) adults from the Cardiovascular Health Study (CHS) and examined associations with baseline CVD risk factors, subclinical CVD, and incident CVD events. We also performed a genome-wide association study for sIL-2Rα in CHS (2964 EAs and 683 AAs) and further combined CHS EA results with those from two other EA cohorts in a meta-analysis (n=4464 EAs). In age, sex- and race- adjusted models, sIL-2Rα was positively associated with current smoking, type 2 diabetes mellitus, hypertension, insulin, waist circumference, C-reactive protein, IL-6, fibrinogen, internal carotid wall thickness, all-cause mortality, CVD mortality, and incident CVD, stroke, and heart failure. When adjusted for baseline CVD risk factors and subclinical CVD, associations with all-cause mortality, CVD mortality, and heart failure remained significant in both EAs and AAs. In the EA genome-wide association study analysis, we observed 52 single-nucleotide polymorphisms in the chromosome 10p15-14 region, which contains IL2RA, IL15RA, and RMB17, that reached genome-wide significance (P<5×10(-8)). The most significant single-nucleotide polymorphism was rs7911500 (P=1.31×10(-75)). The EA meta-analysis results were highly consistent with CHS-only results. No single-nucleotide polymorphisms reached statistical significance in the AAs. CONCLUSIONS: These results support a role for sIL-2Rα in atherosclerosis and provide evidence for multiple-associated single-nucleotide polymorphisms at chromosome 10p15-14.

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Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

October 2015

Volume

35

Issue

10

Start / End Page

2246 / 2253

Location

United States

Related Subject Headings

  • Survival Analysis
  • Sex Distribution
  • Risk Assessment
  • Prospective Studies
  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Interleukin-2 Receptor alpha Subunit
 

Citation

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Chicago
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MLA
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Durda, P., Sabourin, J., Lange, E. M., Nalls, M. A., Mychaleckyj, J. C., Jenny, N. S., … Lange, L. A. (2015). Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan. Arterioscler Thromb Vasc Biol, 35(10), 2246–2253. https://doi.org/10.1161/ATVBAHA.115.305289
Durda, Peter, Jeremy Sabourin, Ethan M. Lange, Mike A. Nalls, Josyf C. Mychaleckyj, Nancy Swords Jenny, Jin Li, et al. “Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan.Arterioscler Thromb Vasc Biol 35, no. 10 (October 2015): 2246–53. https://doi.org/10.1161/ATVBAHA.115.305289.
Durda P, Sabourin J, Lange EM, Nalls MA, Mychaleckyj JC, Jenny NS, et al. Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan. Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2246–53.
Durda, Peter, et al. “Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan.Arterioscler Thromb Vasc Biol, vol. 35, no. 10, Oct. 2015, pp. 2246–53. Pubmed, doi:10.1161/ATVBAHA.115.305289.
Durda P, Sabourin J, Lange EM, Nalls MA, Mychaleckyj JC, Jenny NS, Li J, Walston J, Harris TB, Psaty BM, Valdar W, Liu Y, Cushman M, Reiner AP, Tracy RP, Lange LA. Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan. Arterioscler Thromb Vasc Biol. 2015 Oct;35(10):2246–2253.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

October 2015

Volume

35

Issue

10

Start / End Page

2246 / 2253

Location

United States

Related Subject Headings

  • Survival Analysis
  • Sex Distribution
  • Risk Assessment
  • Prospective Studies
  • Proportional Hazards Models
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Kaplan-Meier Estimate
  • Interleukin-2 Receptor alpha Subunit