Title : Triglyceride-lowering LPL alleles combined with LDL-C-lowering alleles are associated with an additively improved lipoprotein profile - Ibi_2021_Atherosclerosis__ |
Author(s) : Ibi D , Blauw LL , Noordam R , Dolle MET , Jukema JW , Rosendaal FR , Christodoulides C , Neville MJ , Koivula R , Rensen PCN , Karpe F , van Dijk KW |
Ref : Atherosclerosis , : , 2021 |
Abstract :
BACKGROUND AND AIMS: Mendelian randomization studies have shown that triglyceride (TG)- lowering lipoprotein lipase (LPL) alleles and low-density lipoprotein-cholesterol (LDL-C)-lowering alleles have independent beneficial associations on cardiovascular disease (CVD) risk. We aimed to provide further insight into this observation by applying Mendelian randomization analyses of genetically-influenced TG and LDL-C levels on plasma metabolomic profiles. METHODS: We quantified over 100 lipoprotein metabolomic measures in the Netherlands Epidemiology of Obesity (NEO) study (N = 4838) and Oxford Biobank (OBB) (N = 6999) by nuclear magnetic resonance (NMR) spectroscopy. Weighted genetic scores for TG via five LPL alleles and LDL-C via 19 alleles were calculated and dichotomized by the median, resulting in four genotype combinations of high/low TG and high/low LDL-C. We performed linear regression analyses using a two x two design with the group with genetically-influenced high TG and LDL-C as a reference. RESULTS: Compared to the individual groups with genetically-influenced lower TG or lower LDL-C only, the group with combined genetically-influenced lower TG and LDL-C showed an overall independent and additive pattern of changes in metabolomic measures. Over 100 measures were different (p < 1.35 x 10(-3)) compared to the reference, with effect sizes and directionality being similar in NEO and OBB. Most notably, levels of all very-low density lipoprotein (VLDL) and LDL sub-particles were lower. CONCLUSIONS: Our findings provide evidence that TG-lowering on top of LDL-C-lowering has additive beneficial effects on the lipoprotein profile compared to TG-lowering or LDL-C-lowering only, which is in accordance with reported additive genetic effects on CVD risk reduction. |
PubMedSearch : Ibi_2021_Atherosclerosis__ |
PubMedID: 34053745 |
Ibi D, Blauw LL, Noordam R, Dolle MET, Jukema JW, Rosendaal FR, Christodoulides C, Neville MJ, Koivula R, Rensen PCN, Karpe F, van Dijk KW (2021)
Triglyceride-lowering LPL alleles combined with LDL-C-lowering alleles are associated with an additively improved lipoprotein profile
Atherosclerosis
:
Ibi D, Blauw LL, Noordam R, Dolle MET, Jukema JW, Rosendaal FR, Christodoulides C, Neville MJ, Koivula R, Rensen PCN, Karpe F, van Dijk KW (2021)
Atherosclerosis
: