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APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial.

ABSTRACT: The apolipoprotein A5 gene (APOA5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies.We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial.The current analyses were secondary analyses of a data set from the Pounds Lost Trial. We genotyped APOA5 rs964184 in 734 overweight or obese adults who were randomly assigned to one of 4 diets that differed in percentages of energy derived from fat, protein, and carbohydrate for 2 y. We evaluated changes in fasting serum concentrations of total cholesterol (TC), LDL cholesterol, HDL cholesterol, and triglyceride from baseline to 2 y of follow-up.After a 2-y dietary intervention, we showed significant interactions between the APOA5 rs964184 polymorphism and dietary fat intake (low compared with high) in the determination of changes in TC, LDL cholesterol, and HDL cholesterol (P-interaction = 0.007, 0.017, and 0.006, respectively). In the low-fat intake group (20% of energy derived from fat), carriers of the risk allele (G allele) exhibited greater reductions in TC and LDL cholesterol than did noncarriers (P = 0.036 and 0.039, respectively), whereas in the high-fat diet group (40% of energy derived from fat), participants with the G allele had a greater increase in HDL cholesterol than did participants without this allele (P = 0.038).Our data showed better improvement in lipid profiles from long-term low-fat diet intake in the APOA5 rs964184 risk allele.

SUBMITTER: Zhang X

PROVIDER: S-EPMC3441115 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial.

Zhang Xiaomin X Qi Qibin Q Bray George A GA Hu Frank B FB Sacks Frank M FM Qi Lu L

The American journal of clinical nutrition 20120822 4

<h4>Background</h4>The apolipoprotein A5 gene (APOA5) is a major gene that regulates lipid metabolism and is modulated by dietary factors. A novel variant rs964184 in APOA5 was identified to be associated with lipids in genome-wide association studies.<h4>Objective</h4>We examined whether this variant modified changes in lipid concentrations in response to a 2-y weight-loss diet intervention in a randomized trial.<h4>Design</h4>The current analyses were secondary analyses of a data set from the ...[more]

PMID: 22914552

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Project description:BackgroundThioredoxin Interacting Protein (TXNIP) functions as a master regulator for glucose homeostasis. Hypomethylation at the 5'-cytosine-phosphate-guanine-3' (CpG) site cg19693031 of TXNIP has been consistently related to islet dysfunction, hyperglycemia, and type 2 diabetes. DNA methylation (DNAm) may reveal the missing mechanistic link between obesity and type 2 diabetes. We hypothesize that baseline DNAm level at TXNIP in blood may be associated with glycemic traits and their changes in response to weight-loss diet interventions.MethodsWe included 639 adult participants with overweight or obesity, who participated in a 2-year randomized weight-loss diet intervention. Baseline blood DNAm levels were profiled by high-resolution methylC-capture sequencing. We defined the regional DNAm level of TXNIP as the average methylation level over CpGs within 500 bp of cg19693031. Generalized linear regression models were used for main analyses.ResultsWe found that higher regional DNAm at TXNIP was significantly correlated with lower fasting glucose, HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) at baseline (P < 0.05 for all). Significant interactions were observed between dietary protein intake and DNAm on changes in insulin (P-interaction = 0.007) and HOMA-IR (P-interaction = 0.009) at 6 months. In participants with the highest tertile of regional DNAm at TXNIP, average protein (15%) intake was associated with a greater reduction in insulin (β: -0.14; 95% CI: -0.24, -0.03; P = 0.011) and HOMA-IR (β: -0.15; 95% CI: -0.26, -0.03; P = 0.014) than high protein (25%) intake, whereas no significant associations were found in those with the lower tertiles (P > 0.05). The interaction was attenuated to be non-significant at 2 years, presumably related to decreasing adherence to the diet intervention.ConclusionsOur data indicate that higher regional DNAm level at TXNIP was significantly associated with better fasting glucose, HbA1c, and HOMA-IR; and people with higher regional DNAm levels benefited more in insulin and HOMA-IR improvement by taking the average-protein weight-loss diet.

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Dataset Information

APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial.

Publications

APOA5 genotype modulates 2-y changes in lipid profile in response to weight-loss diet intervention: the Pounds Lost Trial.

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