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BackgroundFenofibrate (Fb) is a known treatment for elevated triglyceride (TG) levels. The Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study was designed to investigate potential contributors to the effects of Fb on TG levels. Here, we summarize the analyses of 8 papers whose authors had access to the GOLDN data and were grouped together because they pursued investigations into Fb treatment responses as part of GAW20. These papers report explorations of a variety of genetics, epigenetics, and study design questions. Data regarding treatment with 160 mg of micronized Fb per day for 3 weeks included pretreatment and posttreatment TG and methylation levels (ML) at approximately 450,000 epigenetic markers (cytosine-phosphate-guanine [CpG] sites). In addition, approximately 1 million single-nucleotide polymorphisms (SNPs) were genotyped or imputed in each of the study participants, drawn from 188 pedigrees.ResultsThe analyses of a variety of subsets of the GOLDN data used a number of analytic approaches such as linear mixed models, a kernel score test, penalized regression, and artificial neural networks.ConclusionsResults indicate that (a) CpG ML are responsive to Fb; (b) CpG ML should be included in models predicting the TG level responses to Fb;

Abstract Background Fenofibrate (Fb) is a known treatment for elevated triglyceride (TG) levels. The Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study was designed to investigate potential contributors to the effects of Fb on TG levels. Here, we summarize the analyses of 8 papers whose authors had access to the GOLDN data and were grouped together because they pursued investigations into Fb treatment responses as part of GAW20. These papers report explorations of a variety of genetics, epigenetics, and study design questions. Data regarding treatment with 160 mg of micronized Fb per day for 3 weeks included pretreatment and posttreatment TG and methylation levels (ML) at approximately 450,000 epigenetic markers (cytosine-phosphate-guanine [CpG] sites). In addition, approximately 1 million single-nucleotide polymorphisms (SNPs) were genotyped or imputed in each of the study participants, drawn from 188 pedigrees. Results The analyses of a variety of subsets of the GOLDN data used a number of analytic approaches such as linear mixed models, a kernel score test, penalized regression, and artificial neural networks. Conclusions Results indicate that (a) CpG ML are responsive to Fb; (b) CpG ML should be included in models predicting the TG level responses to Fb; (c) common and rare variants are associated with TG responses to Fb; (d) the interactions of common variants and CpG ML should be included in models predicting the TG response; and (e) sample size is a critical factor in the successful construction of predictive models representing the response to Fb.

Background Previous studies have suggested that for clinical purposes, subjects with fasting triglycerides (TGs) between 89–180 mg/dl (1–2 mmol/l) would benefit from postprandial TGs testing. Objective To determine the postprandial TG response in 2 independent studies and validate who should benefit diagnostically from an oral-fat tolerance test (OFTT) in clinical practice. Methods A population of 1002 patients with coronary heart disease (CHD) from the CORDIOPREV clinical trial and 1115 white US subjects from the GOLDN study underwent OFTTs. Subjects were classified into 3 groups according to fasting cut points of TGs to predict the usefulness of OFTT: (1) TG < 89 mg/dl (<1 mmol/l); (2) TG, 89–180 mg/dl (1–2 mmol/l); and (3) TG > 180 mg/dl (>2 mmol/l). Postprandial TG concentration at any point > 220 mg/dl (>2.5 mmol/l) has been pre-established as an undesirable postprandial response. Results Of the total, 49% patients with CHD and 42% from the general population showed an undesirable response after the OFTT. The prevalence of undesirable postprandial TG in the CORDIOPREV clinical trial was 12.8, 50.3, and 89.7%, in group 1, 2, and 3, respectively ( P < .001) and 11.2, 58.1, and 97.5% in group 1, 2, and 3, respectively ( P < .001) in the GOLDN study. Conclusions These two studies validate the predictive values reported in a previous consensus. Moreover, the findings of the CORDIOPREV and GOLDN studies show that an OFTT is useful to identify postprandial hyperlipidemia in subjects with fasting TG between 1–2 mmol/l (89–180 mg/dL), because approximately half of them have hidden postprandial hyperlipidemia, which may influence treatment. An OFTT does not provide additional information regarding postprandial hyperlipidemia in subjects with low TG (<1 mmol/l, <89 mg/dL) or increased TG (>2 mmol/l, >180 mg/dl). [ABSTRACT FROM AUTHOR]