Journal
HUMAN MOLECULAR GENETICS
Volume 26, Issue 2, Pages 430-437Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddw396
Keywords
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Funding
- University of Hong Kong Foundation for Educational Development and Research [SN/1f/HKUF-DC, C20400.28505200]
- Health Medical Research Fund in Hong Kong [HMRF/12133631]
- Guangzhou Public Health Bureau [201102A211004011]
- Guangzhou Science and Technology Bureau, Guangzhou, China [2002Z2-E2051, 2012J5100041, 2013J4100031]
- University of Birmingham, UK
- Hong Kong Research Grant Council: Theme Based Research Scheme [T12-705/11]
- Hong Kong Research Grant Council: Collaborative Research Fund [HKU2/CRF/12R]
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Observational studies of the association of alanine aminotransferase (ALT) levels with ischaemic heart disease (IHD) and cardiovascular disease (CVD) risk factors are inconsistent, probably because of confounding and reverse causality. Mendelian randomization (MR) provides less confounded results. We used MR analysis to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors. We used instrumental variable analysis based on two single nucleotide polymorphism (SNPs) HSD17B13/MAPK10 (rs6834314) and PNPLA3/SAMM50 (rs738409) to assess the associations of ALT (U/L) with IHD, diabetes and other CVD risk factors in the Guangzhou Biobank Cohort Study (GBCS). Observationally in 19,925 participants ALT levels were strongly positively associated with self-reported IHD, systolic and diastolic blood pressure, low-density lipoprotein-and total cholesterol, triglycerides, fasting glucose, body mass index, waist circumference, heart rate (HR) and diabetes, but were not associated with uncorrected QT interval, HR-corrected QT interval or high-density lipoprotein-cholesterol. In the MR study, using a credible genetic instrument (F-statistic - 23) for ALT, ALT levels were negatively associated with IHD (odds ratio (OR) 0.92, 95% confidence interval (CI) 0.87 to 0.97) and triglycerides (beta - 0.08, 95% CI - 0.13 to - 0.03), but were not associated with other CVD risk factors. Our results using Mendelian randomization suggest that ALT reduces the risk of IHD, probably through reducing triglyceride levels. The underlying mechanisms deserve further investigation.
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