Hypertension and Cardiovascular Disease, Department of Clinical Sciences-Malmö, Lund University, Malmö, Sweden.
Lund University Diabetes Centre, Skåne University Hospital, Malmö, Sweden.
PLoS One. 2018 Nov 8;13(11):e0206974. doi: 10.1371/journal.pone.0206974. eCollection 2018.
Our aim was to identify serum microRNAs (miRNAs) in healthy humans which associate with future onset of both diabetes mellitus and cardiovascular disease. We performed global profiling of 753 mature human miRNAs in serum of 12 pilot subjects followed by measurement of 47 consistently expressed miRNAs in fasting serum of 553 healthy subjects from the baseline exam (1991-1994) of the population based Malmö Diet and Cancer Study Cardiovascular Cohort (MDC-CC), of whom 140 developed diabetes, and 169 cardiovascular diseases during follow-up. We used multivariate logistic regression to test individual miRNAs for association with incident diabetes and cardiovascular disease as compared to control subjects (n = 259). After Bonferroni correction and adjustment for age and sex, each SD increment of log-transformed miR-483-5p was significantly associated with both incident diabetes (OR = 1.48; 95% CI 1.18-1.84, P = 0.001) and cardiovascular disease (OR = 1.40; 95% CI 1.15, 1.72, P = 0.001). In cross sectional analysis, miR-483-5p was correlated with BMI (r = 0.162, P = 0.0001), fasting insulin (r = 0.156, P = 0.0002), HDL (r = -0.099, P = 0.02) and triglycerides (r = 0.11, P = 0.01). Adjustment for these metabolic risk factors, as well as traditional risk factors attenuated the miR-483-5p association with incident diabetes (OR = 1.28 95% CI 1.00-1.64, P = 0.049) whereas its association with incident cardiovascular disease remained virtually unchanged (OR = 1.46 95% CI, 1.18-1.81, P = 0.0005). In conclusion, miR-483-5p associates with both diabetes and cardiovascular disease. The association with diabetes seems partly mediated by obesity and insulin resistance, whereas the association with incident cardiovascular disease is independent of these metabolic factors and traditional cardiovascular disease risk factors.
我们的目的是鉴定健康人群血清中与糖尿病和心血管疾病未来发病相关的 microRNAs（miRNAs）。我们对 12 名先导受试者的 753 个人类成熟 miRNA 进行了全局分析，随后对来自基于人群的马尔默饮食与癌症研究心血管队列（MDC-CC）基线检查（1991-1994 年）的 553 名健康受试者的空腹血清中 47 个持续表达的 miRNA 进行了测量，其中 140 人在随访期间发生了糖尿病，169 人发生了心血管疾病。我们使用多变量逻辑回归来测试个体 miRNA 与新发糖尿病和心血管疾病的关联，与对照受试者（n=259）进行比较。经过 Bonferroni 校正和年龄与性别调整后，miR-483-5p 的对数转换每增加一个标准差与新发糖尿病（OR=1.48；95%CI 1.18-1.84，P=0.001）和心血管疾病（OR=1.40；95%CI 1.15，1.72，P=0.001）显著相关。在横断面分析中，miR-483-5p 与 BMI（r=0.162，P=0.0001）、空腹胰岛素（r=0.156，P=0.0002）、HDL（r=-0.099，P=0.02）和甘油三酯（r=0.11，P=0.01）呈正相关。调整这些代谢危险因素以及传统危险因素后，miR-483-5p 与新发糖尿病的相关性减弱（OR=1.28，95%CI 1.00-1.64，P=0.049），而其与新发心血管疾病的相关性几乎保持不变（OR=1.46，95%CI，1.18-1.81，P=0.0005）。总之，miR-483-5p 与糖尿病和心血管疾病均相关。与糖尿病的相关性部分由肥胖和胰岛素抵抗介导，而与新发心血管疾病的相关性与这些代谢因素和传统心血管疾病危险因素无关。
