Abstract P020: Triglyceride-lowering Lipoprotein Lipase Gene Variants And Improvements In Lipids And Lipoprotein Subspecies Defined By Apolipoprotein C-iii: Pounds Lost Trial

Abstract

Introduction: Triglyceride-lowering variants in the lipoprotein lipase ( LPL ) gene have been associated with a lower risk of coronary heart disease. Lipoproteins are heterogeneous, and lipoprotein subspecies containing apolipoprotein C-III (ApoCIII) have adverse effects on cardiovascular disease (CVD) risk. Hypothesis: We examined associations of triglyceride-lowering LPL gene variants with long-term improvement in lipids and lipoprotein subspecies with ApoCIII in patients with obesity. We also investigated whether the LPL gene variants were significantly related to the improvement of the 10-year CVD risk estimated using the Framingham risk score in the participants of a weight-loss dietary intervention trial. Methods: This study included 382 overweight and obese adults of white European ancestry in a 2-year weight-loss dietary intervention, the POUNDS Lost trial. We evaluated changes in lipids (triglycerides and cholesterol) and lipoproteins (such as very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)) subfractions defined by the presence or absence of ApoCIII from baseline to 2 years after the intervention. A genetic risk score of LPL (LPL-GRS) was calculated by summing triglyceride-lowering alleles of five independent single nucleotide polymorphisms (SNPs). We calculated the Framingham risk score and estimated changes in the 10-year CVD risk after the intervention. Results: At baseline, higher scores of triglyceride-lowering LPL-GRS were significantly associated with higher levels of HDL cholesterol (p= 0.0065) and lower levels of triglycerides (p= 0.017). Higher LPL-GRS was also associated with more decreases in total triglycerides (p= 0.028) and triglycerides in VLDL with ApoCIII (p=0.018) at 2 years. The LPL-GRS was also predictive of 2-year improvements in other atherogenic lipoprotein subtypes, such as cholesterol in VLDL with ApoCIII (p= 0.037) and cholesterol in LDL with ApoCIII (p= 0.027) after the intervention. Further, the LPL-GRS was significantly associated with a 2-year reduction of the estimated CVD risk, regardless of the initial risk status (p=0.034). Conclusion: The triglyceride-lowering LPL-GRS was significantly predictive of improvements in unfavorable lipid profiles, including lipoprotein subtypes containing ApoCIII after consuming a weight-loss diet in patients with obesity. The reduction of the estimated CVD risk after the dietary intervention was predicted by the LPL-GRS at the pre-intervention.