TY - JOUR T1 - Plasma Levels of Soluble Interleukin-2 Receptor α: Associations With Clinical Cardiovascular Events and Genome-Wide Association Scan. JF - Arterioscler Thromb Vasc Biol Y1 - 2015 A1 - Durda, Peter A1 - Sabourin, Jeremy A1 - Lange, Ethan M A1 - Nalls, Mike A A1 - Mychaleckyj, Josyf C A1 - Jenny, Nancy Swords A1 - Li, Jin A1 - Walston, Jeremy A1 - Harris, Tamara B A1 - Psaty, Bruce M A1 - Valdar, William A1 - Liu, Yongmei A1 - Cushman, Mary A1 - Reiner, Alex P A1 - Tracy, Russell P A1 - Lange, Leslie A KW - Adult KW - African Americans KW - Age Distribution KW - Aged KW - Cardiovascular Diseases KW - Cohort Studies KW - Coronary Artery Disease KW - Female KW - Genetic Predisposition to Disease KW - Genome-Wide Association Study KW - Humans KW - Incidence KW - Interleukin-2 Receptor alpha Subunit KW - Kaplan-Meier Estimate KW - Male KW - Middle Aged KW - Polymorphism, Single Nucleotide KW - Proportional Hazards Models KW - Prospective Studies KW - Risk Assessment KW - Sex Distribution KW - Survival Analysis AB -

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.

VL - 35 IS - 10 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26293465?dopt=Abstract ER -