The effect of leptin on blood pressure considering smoking status: a Mendelian randomization study

Studies on leptin and blood pressure (BP) associations have yielded inconsistent findings. The current study aimed to evaluate the effect of genetically determined leptin on BP and to explore whether smoking status modified this effect. We conducted a Mendelian randomization analysis using the baseline data of 3860 participants in the Framingham Heart Study 3rd generation cohort. Pairwise associations among leptin genetic risk score (GRS), log-transformed leptin (log-leptin), and BP were assessed by multivariate linear regression models. Age and sex were adjusted in the base model, and education, smoking, drinking, and physical activity were adjusted in the full model. The interaction between leptin GRS and smoking was evaluated by adding an interaction term, GRS × smoking, in the fully adjusted model. In the age- and sex-adjusted analyses, log-leptin was positively associated with systolic BP (SBP) (P = 2.35 × 10^-79), diastolic BP (DBP) (P = 6.19 × 10^-76), mean arterial pressure (MAP) (P = 1.10 × 10^-90), and pulse pressure (P = 4.38 × 10^-19). Leptin GRS significantly increased log-leptin (P = 0.00001). Leptin GRS was associated with reduced SBP (P = 0.04), DBP (P = 0.006), and MAP (P = 0.008) among current smokers. In the fully adjusted model, significant interactions between GRS and smoking were identified for SBP (P = 0.02), DBP (P = 0.002), and MAP (P = 0.003). Sensitivity analyses among participants not taking antihypertensive or glucose-lowering medications revealed similar associations. Our study provided evidence for a potentially causal relationship between leptin and BP among current smokers.