Xu Lin, Jiang Chao Qiang, Lam Tai Hing, Zhang Wei Sen, Zhu Feng, Jin Ya Li, Thomas G Neil, Cheng Kar Keung, Schooling C Mary
School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Guangzhou 12th Hospital, Guangzhou, People's Republic of China.
Hum Mol Genet. 2017 Jan 15;26(2):430-437. doi: 10.1093/hmg/ddw396.
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 (β - 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.
丙氨酸氨基转移酶（ALT）水平与缺血性心脏病（IHD）及心血管疾病（CVD）风险因素之间关联的观察性研究结果并不一致，这可能是由于存在混杂因素和反向因果关系。孟德尔随机化（MR）分析能提供受混杂因素影响较小的结果。我们采用MR分析来评估ALT（单位：U/L）与IHD、糖尿病及其他CVD风险因素之间的关联。在广州生物样本库队列研究（GBCS）中，我们基于两个单核苷酸多态性（SNP），即HSD17B13/MAPK10（rs6834314）和PNPLA3/SAMM50（rs738409），运用工具变量分析来评估ALT（U/L）与IHD、糖尿病及其他CVD风险因素之间的关联。在19,925名参与者中进行观察性研究发现，ALT水平与自我报告的IHD、收缩压和舒张压、低密度脂蛋白胆固醇、总胆固醇、甘油三酯、空腹血糖、体重指数、腰围、心率（HR）及糖尿病呈强正相关，但与未校正的QT间期、心率校正的QT间期或高密度脂蛋白胆固醇无关。在MR研究中，使用针对ALT的可信基因工具（F统计量 = 23），ALT水平与IHD（优势比（OR）0.92，95%置信区间（CI）0.87至0.97）及甘油三酯（β -0.08，95% CI -0.13至 -0.03）呈负相关，但与其他CVD风险因素无关。我们使用孟德尔随机化得出的结果表明，ALT可能通过降低甘油三酯水平来降低IHD风险。其潜在机制值得进一步研究。
