Pharmacogenomics of statins: lipid response and other outcomes in Brazilian cohorts

Author(s):  
Carolina Dagli-Hernandez ◽  
Yitian Zhou ◽  
Volker Martin Lauschke ◽  
Fabiana Dalla Vecchia Genvigir ◽  
Thiago Dominguez Crespo Hirata ◽  
...  
Keyword(s):  
2008 ◽  
Vol 37 (5) ◽  
pp. 327-334 ◽  
Author(s):  
M. J. Tikkanen ◽  
C-F. Xu ◽  
T. Hämäläinen ◽  
P. Talmud ◽  
S. Sarna ◽  
...  

Circulation ◽  
2002 ◽  
Vol 105 (16) ◽  
pp. 1904-1908 ◽  
Author(s):  
Treva Rice ◽  
Jean-Pierre Després ◽  
Louis Pérusse ◽  
Yuling Hong ◽  
Michael A. Province ◽  
...  

2018 ◽  
Vol 59 (4) ◽  
pp. 722-729 ◽  
Author(s):  
Xin Geng ◽  
Marguerite R. Irvin ◽  
Bertha Hidalgo ◽  
Stella Aslibekyan ◽  
Vinodh Srinivasasainagendra ◽  
...  

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P < 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Claire E Berryman ◽  
Jessica A Grieger ◽  
Sheila G West ◽  
George H Rothblat ◽  
Jun Zhang ◽  
...  

Introduction: Epidemiological and clinical evidence demonstrate benefits of walnuts on cardiometabolic risk factors. Hypothesis: Previously, we conducted a study that evaluated the acute, postprandial effects of walnut components [separated nut skins (5.6 g), de-fatted nutmeat (34 g), and nut oil (51 g)] versus whole walnuts (85 g) on lipid/lipoprotein responses and other measures of CVD risk. The results reported herein are from an ancillary study that compared postprandial whole walnut values to fasting values, to test the hypothesis that the whole walnut treatment would improve reverse cholesterol transport. Methods: A randomized 4-period crossover design was conducted with healthy overweight and obese adults (n=15; 9 women and 6 men) with moderate hypercholesterolemia. Plasma lipids were measured at 0 (fasting), 30, 60, 120, 240, and 360 min post meal consumption; serum for ex vivo cholesterol efflux analysis was collected at 0 and 240 min. The mean fractional efflux of radiolabeled cholesterol was conducted in J774 macrophage cells cultured with 2.5% human serum. Results: A mixed linear model demonstrated an increase in TG postprandially (P < 0.01). TG levels were significantly increased at 120, 240, and 360 min compared to baseline (30.1 ± 5.1 mg/dl, 42.7 ± 5.2 mg/dl, 21.1 ± 5.1 mg/dl, respectively; P < 0.01 for all). HDL-C and the total cholesterol:HDL-C (TC:HDL) ratio also increased postprandially (P = 0.04 and P < 0.01, respectively). HDL-C increased at 60 min (1.8 ± 0.7 mg/dl; P = 0.01) and TC:HDL increased at 120, 240, and 360 min (0.2 ± 0.1, 0.3 ± 0.1, 0.3 ± 0.1, respectively; P < 0.01 for all) compared to baseline. Cholesterol efflux was increased by 3.3 % in cells cultured with postprandial serum relative to fasting baseline (baseline: 18.6 ± 0.3 %, 240 min: 19.2 ± 0.3 %; P = 0.02). Cholesterol efflux correlated positively with plasma HDL-C concentrations (r = 0.43; P = 0.02). Conclusion: Acute consumption of walnuts increased ex vivo cholesterol efflux, suggesting a novel mechanism by which walnut consumption may reduce cardiovascular risk.


1991 ◽  
pp. 128-129
Author(s):  
Peter Allhoff ◽  
Ulrich Laaser ◽  
Joachim Heinrich

2013 ◽  
Vol 110 (5) ◽  
pp. 790-796 ◽  
Author(s):  
Lena K. Brahe ◽  
Lars Ängquist ◽  
Lesli H. Larsen ◽  
Karani S. Vimaleswaran ◽  
Jörg Hager ◽  
...  

Blood lipid response to a given dietary intervention could be determined by the effect of diet, gene variants or gene–diet interactions. The objective of the present study was to investigate whether variants in presumed nutrient-sensitive genes involved in lipid metabolism modified lipid profile after weight loss and in response to a given diet, among overweight European adults participating in the Diet Obesity and Genes study. By multiple linear regressions, 240 SNPs in twenty-four candidate genes were investigated for SNP main and SNP–diet interaction effects on total cholesterol, LDL-cholesterol, HDL-cholesterol and TAG after an 8-week low-energy diet (only main effect), and a 6-monthad libitumweight maintenance diet, with different contents of dietary protein or glycaemic index. After adjusting for multiple testing, a SNP–dietary protein interaction effect on TAG was identified for lipin 1 (LPIN1) rs4315495, with a decrease in TAG of − 0·26 mmol/l per A-allele/protein unit (95 % CI − 0·38, − 0·14,P= 0·000043). In conclusion, we investigated SNP–diet interactions for blood lipid profiles for 240 SNPs in twenty-four candidate genes, selected for their involvement in lipid metabolism pathways, and identified one significant interaction betweenLPIN1rs4315495 and dietary protein for TAG concentration.


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