Abstract P134: Genome-wide Association Study of Heart Rate Response to Mental Stress

• Published in: Circulation (New York, N.Y.) Vol. 137; no. suppl_1
• Main Authors: Huang, Yunfeng, Hui, Qin, Hammadah, Muhammad, Pimple, Pratik M, Al Mheid, Ibhar, Wilmot, Kobina, Ramadan, Ronnie, Shah, Amit J, Pearce, Brad, Garcia, Ernest V, Kutner, Michael, Bremner, J. Douglas, Esteves, Fabio, Raggi, Paolo, Sheps, David S, Vaccarino, Viola, Quyyumi, Arshed A, Sun, Yan
• Format: Journal Article
• Language: English
• Published: 20.03.2018
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circ.137.suppl_1.p134

Abstract only Ischemia results from an imbalance between myocardial oxygen supply and demand. Ischemia associated with mental stress (MS) has been associated with adverse outcomes in patients with coronary artery diseases (CAD). Higher heart rate (HR) and blood pressure responses to MS are associated with a greater likelihood of MS-induced ischemia. Although multiple genetic loci have been associated with baseline HR, genetic associations for HR responses to MS remain unknown. We aimed to discover the genetic determinants of HR response to MS in a bi-ethnic population. A sample of 499 Caucasian and 271 African American patients with CAD were recruited into the Mental Stress Ischemia Prognosis (MIPS) study. Race was defined using genetic ancestry. Genome-wide SNP data were genotyped using Illumina’s Multi-Ethnic Genotyping (MEG) chip and then imputed to the 1000 Genome Project phase 3 panel. Cardiovascular risk factors, demographic, behavioral, and medication history data were obtained by questionnaires and chart reviews. MS was induced by a public speaking task and the HR response to MS was measured as post-stress HR minus pre-stress HR. We conducted genome-wide association analysis of HR response to MS using multiple linear regression adjusted for age, sex, beta-blocker use, the pre-stress HR and ethnicity. A meta-analysis was performed across the two ethnicities. After multiple-testing correction, no significant associations with HR response to MS were identified among Whites .However, fourteen SNPs located in gene ITGA1 with a mean minor allele frequency of 36.5% (range: 36.3% - 37.1%) were significantly associated with the HR response to MS in Blacks (meta-analysis p<5х10 -8 ). The minor alleles of all 14 variants were associated with a higher HR response. On average heterozygotic and homozygotic Blacks of the minor allele in any of these SNPs have a 4.558 beat/min (range: 4.514 – 4.659 beat/min) and 9.116 beat/min (range: 9.028 – 9.318 beat/min) increase in HR response to MS, correspondingly. The ITGA1 gene encodes the alpha-1 subunit of integrin receptors. This protein heterodimerizes with the beta-1 subunit to form a cell-surface receptor for collagen and laminin. The heterodimeric receptor is involved in cell-cell adhesion and may play a role in inflammation and fibrosis. Further functional studies to follow up these genetic loci may provide insight into regulatory mechanisms of HR response to mental stress that may be prognostically informative for CAD patients.