Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia

Abstract

The acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2 catalyze the final step in triglycerides biosynthesis. This study examined the relationships of baseline phenotypes and the common polymorphisms in DGAT1 and DGAT2 with the lipid responses to niacin.Lipid responses in Chinese patients with dyslipidemia treated with the extended release (ER) niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks (n = 121, the primary study) or with ER niacin 1500 mg for at least 4 weeks (n = 68, the replication study) were analyzed according to genotypes of DGAT1 rs7003945 T>C and DGAT2 rs3060 T>C polymorphisms.Treatment with ER niacin improved all lipid parameters in both studies. Absolute and percentage changes in lipids were related to their baseline levels, particularly for low-density lipoprotein cholesterol (LDL-C). The DGAT2 rs3060 T>C polymorphism was associated with lower baseline LDL-C, apoB, high-density lipoprotein cholesterol (HDL-C), and apoAI in patients on statin therapy in the primary study. Subjects with the DGAT2 rs3060 T>C variant had less reduction in LDL-C in the primary study and smaller changes in triglyceride and HDL-C in the replication study but these associations became non-significant after adjusting for baseline lipid values. The DGAT1 rs7003945 T>C polymorphism was not related to lipid baseline values or changes in either study. Concomitant statin therapy and lower body weight were also associated with greater reduction in LDL-C.Baseline lipid levels were the main determinants of lipid responses especially for LDL-C. The DGAT2 rs3060 polymorphism might influence the lipid responses depending on baseline phenotype, but this association did not persist after adjustment for the baseline lipid levels.

Donor PPARα Gene Polymorphisms Influence the Susceptibility to Glucose and Lipid Disorders in Liver Transplant Recipients

“…In addition to clinical parameters, genetic factors also play important roles in the development of human diseases. 4 The peroxisome proliferator-activated receptors (PPARs), which compose a subfamily of nuclear hormone receptors, have long been considered to be key regulators of metabolic status. 5 , 6 Particularly in the liver, PPARs regulate a whole spectrum of physiological functions, including lipid and glucose metabolism, cholesterol and bile acid homeostasis, insulin sensitivity, inflammatory responses, and regenerative mechanisms.…”

Management of Familial Hypercholesterolemia in Hong Kong

“…This feature differs from the LDL-C-lowering effects of statins for which the percentage changes in LDL-C levels are largely independent of baseline values. Indeed, we found that patients with FH had greater reductions in LDL-C levels with niacin/laropiprant than those without FH because of high baseline LDL-C levels 60) . In some FH patients with high pretreatment LDL-C levels, the LDL-C reduction with niacin was similar in magnitude (~50%) to the effects of PCSK9 inhibitors.…”

“…In a small cohort of study with niacin, we found Chinese patients with FH had a higher level of Lp (a) The clinical use of niacin in the statin era has been challenged after two outcome studies (the AIM-HIGH trial and the HPS2-THRIVE trial), which showed that niacin or a combination of niacin and laropiprant (a selective antagonist of PGD2 at the DP1 receptor to reduce niacin-induced flushing) did not reduce cardiovascular event in patients receiving intensive statin therapy 57,58) . In our previous studies with niacin and niacin/laropiprant, we found the LDL-C response to niacin was significantly associated with baseline LDL-C levels 59,60) . This is in line with the observation in the HPS2-THRIVE study where the percentage reduction in LDL-C levels was dependent on the baseline values and this influenced the cardiovascular outcome with those with baseline LDL-C level of 2 mmol/L having the best outcome and those with LDL-C level of 1.5 mmol/L the worst outcome 58) .…”

Guidance on the management of familial hypercholesterolaemia in Hong Kong: an expert panel consensus viewpoint

“…Niacin can reduce plasma Lp(a) levels by 30% to 40%; notably, the LDL-C level lowering-effect of niacin is largely dependent on baseline LDL-C levels. 31,32 Therefore, if available, niacin may be used in patients with FH who do not reach their target LDL-C levels with statin therapy. Lipoprotein apheresis will also reduce Lp(a) level, but is not readily available in the public hospitals in Hong Kong; however, plasmapheresis is currently used.…”