Affiliation:
1. School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
2. City University of New York, School of Public Health and Health Policy, New York, NY
Abstract
ABSTRACT
Background
Evolutionary biology suggests reproduction trades off against longevity. Genetic selection in favor of fertility and ischemic heart disease (IHD) exists in humans. Observationally, soy protects against IHD. Soy amino acids, glutamate and aspartate, may lower androgens. No large randomized controlled trials testing their health effects exist.
Objective
Using Mendelian randomization, we assessed how genetically predicted glutamate and aspartate affected IHD, blood pressure, and diabetes.
Methods
A separate sample instrumental variable analysis with genetic instruments was used to obtain unconfounded estimates using genetic variants strongly (P < 5 × 10−8) and solely associated with glutamate or aspartate applied to an IHD case (n ≤76,014)–control (n ≤ 264,785) study (based on a meta-analysis of CARDIoGRAMplusC4D 1000 Genomes, UK Biobank CAD SOFT GWAS and Myocardial Infarction Genetics and CARDIoGRAM Exome), blood pressure from the UK Biobank (n ≤ 361,194), and the DIAbetes Genetics Replication And Meta-analysis diabetes case (n = 26,676)–control (n = 132,532) study. A weighted median and MR-Egger were used for a sensitivity analysis.
Results
Glutamate was not associated with IHD, blood pressure, or diabetes after correction for multiple comparisons. Aspartate was inversely associated with IHD (odds ratio (OR) 0.92 per log-transformed standard deviation (SD); 95% confidence interval (CI) 0.88, 0.96) and diastolic blood pressure (−0.03; 95% CI −0.04, −0.02) using inverse variance weighting, but not diabetes (OR 1.00; 95% CI 0.91, 1.09). Associations were robust to the sensitivity analysis.
Conclusions
Our findings suggest aspartate may play a role in IHD and blood pressure, potentially underlying cardiovascular benefits of soy. Clarifying the mechanisms would be valuable for IHD prevention and for defining a healthy diet.
Publisher
Oxford University Press (OUP)
Subject
Nutrition and Dietetics,Medicine (miscellaneous)
Cited by
21 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献