| Title: | Using genetics to examine the overall and sex-specific associations of branch-chain amino acids and the valine metabolite, 3-hydroxyisobutyrate, with ischemic heart disease and diabetes: A two-sample Mendelian randomization study |
| Journal: | Atherosclerosis |
| Published: | 21 Aug 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37660674/ |
| DOI: | https://doi.org/10.1016/j.atherosclerosis.2023.117246 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7615055 |
Publication 7705
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Abstract
BACKGROUND AND AIMS: Branch-chain amino acids (BCAAs) are linked to higher risk of diabetes, whilst the evidence on ischemic heart disease (IHD) is limited. Valine metabolite, 3-hydroxyisobutyrate (3-HIB), also plays an important role in metabolism, whilst its effect has been rarely examined. At the situation of no evidence from large trials, we assessed the role of BCAAs and 3-HIB in IHD and diabetes using Mendelian randomization to minimize confounding. Given their potential role in sex hormones, we also examined sex-specific associations.</p>
METHODS: We used genetic variants to predict BCAAs and 3-HIB, and obtained their associations with IHD and diabetes in large consortia and cohorts, as well as sex-specific association in the UK Biobank and DIAGRAM. We obtained and combined the Wald estimates using inverse variance weighting, and different analytic methods robust to pleiotropy.</p>
RESULTS: Genetically predicted BCAAs were associated with higher risk of IHD (odds ratio (OR) 1.19 per standard deviation (SD) increase in BCAAs, 95% confidence interval (CI) 1.05 to 1.35) and diabetes (OR 1.20, 95% CI 1.08 to 1.34). The associations with IHD were stronger in women (OR 1.23, 95% CI 1.03 to 1.48) than men (OR 0.96, 95% CI 0.83 to 1.10). 3-HIB was associated with higher risk of IHD (OR 1.43, 95% CI 1.17 to 1.73) but not diabetes, with no sex disparity.</p>
CONCLUSION: BCAAs and 3-HIB are potential targets for prevention in IHD and/or diabetes. BCAAs may exert a sex-specific role in IHD. Consideration of the sex disparity and exploration of the underlying pathways would be worthwhile.</p>
3 Authors
- Jie V Zhao
- Bohan Fan
- Stephen Burgess
1 Application
| Application ID | Title |
|---|---|
| 42468 | Non-reproductive effects of endogenous androgen exposures, potential drivers of and downstream factors related to androgens: a Mendelian randomization study in the UK Biobank |
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