Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, CA 92093, USA.
Division of Epidemiology and Biostatistics, School of Public Health, San Diego State University, San Diego, CA 92182, USA.
Int J Environ Res Public Health. 2021 Feb 24;18(5):2225. doi: 10.3390/ijerph18052225.
Non-alcoholic fatty liver disease (NAFLD) is common among 30% of American adults. Former and current smokers are at higher risk for NAFLD compared to never smokers. The ratio of urine caffeine metabolites to caffeine intake-namely, urine caffeine metabolite indices-has previously been used as a proxy for CYP1A2 activity, which is one of the main liver metabolizing enzymes. CYP1A2 activity is associated with NAFLD progression. No studies to our knowledge have examined the associations of liver enzymes, smoking intensity, and secondhand smoke (SES) with CYP1A2 activity (using caffeine metabolite indices) across smoking status. We analyzed national representative samples from the 2009-2010 National Health and Nutrition Examination Survey (NHANES). Interestingly, even within a normal range, several liver enzymes were associated with caffeine metabolite indices, and patterns of many of these associations varied by smoking status. For instance, within a normal range, aspartate aminotransferase (AST) in never smokers and bilirubin in current smokers were inversely associated with 1-methyluric acid and 5-acetylamino-6-amino-3-methyluracil (URXAMU). Furthermore, we observed a common pattern: across all smoking statuses, higher AST/alanine aminotransferase (AST/ALT) was associated with 1-methyluric acid and URXAMU. Moreover, in current smokers, increased lifelong smoking intensity was associated with reduced caffeine metabolite indices, but acute cigarette exposure as measured by SES levels was associated with increased caffeine metabolite indices among never smokers. In summary, commonly used liver enzyme tests can reflect the CYP1A2 activity even within a normal range, but the selection of these enzymes depends on the smoking status; the associations between smoking and the CYP1A2 activity not only depend on the intensity but also the duration of tobacco exposure.
非酒精性脂肪性肝病（NAFLD）在美国成年人中发病率约为 30%。与不吸烟者相比，既往吸烟者和现吸烟者患 NAFLD 的风险更高。尿咖啡因代谢产物与咖啡因摄入量的比值，即尿咖啡因代谢产物指数，以前曾被用作 CYP1A2 活性的替代指标，CYP1A2 是主要的肝脏代谢酶之一。CYP1A2 活性与 NAFLD 的进展有关。据我们所知，尚无研究探讨肝酶、吸烟强度和二手烟（SES）与 CYP1A2 活性（使用咖啡因代谢产物指数）在吸烟状态下的相关性。我们分析了 2009-2010 年全国健康和营养调查（NHANES）的全国代表性样本。有趣的是，即使在正常范围内，几种肝酶也与咖啡因代谢产物指数相关，许多这些关联的模式因吸烟状态而异。例如，在正常范围内，不吸烟者的天冬氨酸转氨酶（AST）和现吸烟者的胆红素与 1-甲基尿酸和 5-乙酰氨基-6-氨基-3-甲基尿嘧啶（URXAMU）呈负相关。此外，我们观察到一种常见模式：在所有吸烟状态下，较高的天冬氨酸转氨酶/丙氨酸转氨酶（AST/ALT）与 1-甲基尿酸和 URXAMU 相关。此外，在现吸烟者中，终身吸烟强度的增加与咖啡因代谢产物指数的降低有关，但 SES 水平衡量的急性香烟暴露与不吸烟者中咖啡因代谢产物指数的增加有关。总之，即使在正常范围内，常用的肝酶检测也可以反映 CYP1A2 活性，但这些酶的选择取决于吸烟状态；吸烟与 CYP1A2 活性之间的关联不仅取决于吸烟强度，还取决于吸烟暴露的持续时间。
