Abstract 4142609: Lifestyle associated-factors influencing serum LDL-C and HDL-C levels and RNA-seq analysis in monozygotic twins of Osaka University Twin Research Registry

Introduction: Lifestyle habits are considered to be significant determinants of serum lipoprotein concentration. There have been many studies on the factors affecting serum LDL cholesterol(LDL-C) or HDL cholesterol(HDL-C) levels, however, most studies have been conducted in unrelated individuals who had different genetic backgrounds, making it difficult to determine which factors affecting lipid profile might be genetic or environmental. Research Questions: Monozygotic(MZ) twins share almost the same genes, so we hypothesize that twin research may allow us to determine factors associated with lipid profile. Aim: The aim is to examine factors that affect LDL-C and HDL-C levels using data of monozygotic twins database including nutrition survey data, anthropometric and biochemical parameters and to identify genes whose expression levels changed in pairs with large within-pair difference of LDL-C or HDL-C. Methods: The database of 263 pairs of MZ twins in the Osaka University Twin Research Center was analyzed. 1. As for the dietary, smoking, exercise, and drinking habits, we confirmed their influences on LDL-C or HDL-C by Wilcoxon’s signed-rank test in the MZ pairs with the different lifestyle habits. 2. We performed a linear regression analysis of 263 pairs to identfy anthropometric and biochemical parameters(BMI, serum TG, TP and HbA1c etc) associated with the difference in LDL-C(ΔLDL-C) and HDL-C(ΔHDL-C). 3. RNA-seq data derived from peripheral blood mononuclear cells of 59 pairs were examined in the group of large ΔLDL-C or ΔHDL-C. Result: 1. LDL-C increased with increased cholesterol intake(n=65 pairs, p<0.05). HDL-C decreased with smoking(n=15 pairs, p<0.05) and increased with exercise (n=23 pairs, p<0.005). 2. Linear regression analysis of 263 pairs showed that ΔLDL-C was significantly associated with age, ΔTG and ΔBMI, and ΔHDL-C was significantly associated with ΔBMI, ΔTG, ΔTP, and ΔLDL-C. 3. In the 20 pairs of larger ΔLDL-C or ΔHDL-C among the total 59 pairs, RNA-seq revealed that the expression of downstream genes of TLR4 and IFNG was suppressed due to increased HDL-C levels in the large difference of ΔHDL-C. Conclusion: Cholesterol intake, aging, and BMI are factors that affect serum LDL-C levels, and smoking, exercise, and BMI are factors that affects serum HDL-C levels in MZ twins. In addition, the subject who had lower HDL-C in twins showed more inflammatory gene expressions in peripheral blood mononuclear cells.