Dataset Information

Genetic, epigenetic and transcriptional variations at NFATC2IP locus with weight loss in response to diet interventions: The POUNDS Lost Trial.

ABSTRACT: DNA Methylation of NFATC2IP was recently identified as being causally related to body mass index. The present study aimed to examine the roles of the genetic variation, methylation and gene expression at this locus in adiposity changes in a 2-year weight-loss trial. Participants (n = 692) were genotyped and randomly assigned to 1 of the 4 reduced-calorie diets, DNA methylation was derived from stored blood samples at baseline (n = 48), and adipose tissue gene expression was measured in 96 volunteers. We found significant interactions of fat intake with the genetic (rs11150675) and transcriptional (ILMN_1725441) variations at the NFATC2IP locus on 2-year weight change (Pinteraction < .01). Similarly, cis-DNA methylation at cg26663590 of the NFATC2IP locus showed an opposite impact on weight-loss in response to high-fat vs low-fat diet (effect size, 4.62 vs -1.24 kg). Additionally, baseline methylation at cg26663590 causally mediated 52.8% of the effect of rs11150675 on 2-year weight-loss in the high-fat diet group (P = .01), whereas no such mediation was observed in the low-fat diet group. Our findings suggest potentially causal effects of genetic, epigenetic and transcriptional variations at the NFATC2IP locus on adiposity changes in response to dietary fat intake.

SUBMITTER: Sun D

PROVIDER: S-EPMC6105429 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Genetic, epigenetic and transcriptional variations at NFATC2IP locus with weight loss in response to diet interventions: The POUNDS Lost Trial.

Sun Dianjianyi D Heianza Yoriko Y Li Xiang X Shang Xiaoyun X Smith Steven R SR Bray George A GA Sacks Frank M FM Qi Lu L

Diabetes, obesity & metabolism 20180524 9

DNA Methylation of NFATC2IP was recently identified as being causally related to body mass index. The present study aimed to examine the roles of the genetic variation, methylation and gene expression at this locus in adiposity changes in a 2-year weight-loss trial. Participants (n = 692) were genotyped and randomly assigned to 1 of the 4 reduced-calorie diets, DNA methylation was derived from stored blood samples at baseline (n = 48), and adipose tissue gene expression was measured in 96 volunt ...[more]

PMID: 29693310

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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.

Dataset Information

Genetic, epigenetic and transcriptional variations at NFATC2IP locus with weight loss in response to diet interventions: The POUNDS Lost Trial.

Publications

Genetic, epigenetic and transcriptional variations at NFATC2IP locus with weight loss in response to diet interventions: The POUNDS Lost Trial.

Similar Datasets

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