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DNA hypermethylation of the serotonin receptor type-2A gene is associated with a worse response to a weight loss intervention in subjects with metabolic syndrome.

ABSTRACT: Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC) with obesity traits and depressive symptoms in individuals with metabolic syndrome (MetS) enrolled in a behavioural weight loss programme. Analyses were based on 41 volunteers (mean age 49 ± 1 year) recruited within the RESMENA study. Depressive symptoms (as determined using the Beck Depression Inventory), anthropometric and biochemical measurements were analysed at the beginning and after six months of weight loss treatment. At baseline, DNA from WBC was isolated and cytosine methylation in the HTR2A gene promoter was quantified by a microarray approach. In the whole-study sample, a positive association of HTR2A gene methylation with waist circumference and insulin levels was detected at baseline. Obesity measures significantly improved after six months of dietary treatment, where a lower mean HTR2A gene methylation at baseline was associated with major reductions in body weight, BMI and fat mass after the treatment. Moreover, mean HTR2A gene methylation at baseline significantly predicted the decrease in depressive symptoms after the weight loss treatment. In conclusion, this study provides newer evidence that hypermethylation of the HTR2A gene in WBC at baseline is significantly associated with a worse response to a weight-loss intervention and with a lower decrease in depressive symptoms after the dietary treatment in subjects with MetS.

SUBMITTER: Perez-Cornago A

PROVIDER: S-EPMC4073158 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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DNA hypermethylation of the serotonin receptor type-2A gene is associated with a worse response to a weight loss intervention in subjects with metabolic syndrome.

Perez-Cornago Aurora A Mansego Maria L ML Zulet María Angeles MA Martinez José Alfredo JA

Nutrients 20140623 6

Understanding the regulation of gene activities depending on DNA methylation has been the subject of much recent study. However, although polymorphisms of the HTR2A gene have been associated with both obesity and psychiatric disorders, the role of HTR2A gene methylation in these illnesses remains uncertain. The aim of this study was to evaluate the association of HTR2A gene promoter methylation levels in white blood cells (WBC) with obesity traits and depressive symptoms in individuals with meta ...[more]

PMID: 24959950

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Project description:Abstract Objectives Choline is an essential nutrient critical for components of the cell membrane, such as choline-containing phospholipids (phosphatidylcholine and sphingomyelin), and in synthesis of the neurotransmitter acetylcholine. Choline has been shown to exert neuroprotective effects, but the association between serum choline and cognitive performance has been scarcely investigated. Our aims are: 1) To study the association between serum total choline, phosphatidylcholine and sphingomyelin with cognitive performance in subjects with metabolic syndrome; and 2) to analyze genetic variants and dietary intake most associated with cholines in this population. Methods We analyzed 426 subjects (aged 55–75 y) with metabolic syndrome from the PREDIMED Plus-Valencia Study. Serum total choline, phosphatidylcholine and sphingomyelin were determined by NMR spectroscopy. Cognitive tests, including verbal fluency (both semantic and phonemic fluency) and the Trail Making Test (TMT) (parts A and B), were administered. Candidate gene polymorphisms were determined by array genotyping. Diet was analyzed by validated questionnaires. Multivariate regression models were fitted. Results Cholines (total, phosphatidylcholine and sphingomyelin) were strongly associated with sex (higher in women; P < 0.001), age (lower at increasing age; P < 0.05) and diabetes (lower in type-2 diabetics; P < 0.01) in a multivariate model. Although the three tested variables presented statistically significant associations with cognition, serum sphingomyelin was the most associated. Thus, in a multivariate model, serum phosphatidylcholine was directly associated with better verbal fluency (P = 0.040 and P = 0.029 for phonemic and semantic, respectively) and inversely associated (lower score mean better performance) with the TMT-A (P = 0.013) and the TMT-B (P = 0.035). In the genetic analysis, we detected several polymorphisms strongly associated with cholines (rs10991629-SLC44A1 with P < 0.005 and rs8068641-PEMT; P < 0.01, among others). We identified several dietary associations as well as gene-diet modulations. Conclusions Phosphatidylcholines are associated with better cognitive function and their levels are modulated by diet and genetics. Funding Sources Generalitat Valenciana (PROMETEO2017/017) and Spanish Ministry of Science (FPU 18/0,1703).

Dataset Information

DNA hypermethylation of the serotonin receptor type-2A gene is associated with a worse response to a weight loss intervention in subjects with metabolic syndrome.

Publications

DNA hypermethylation of the serotonin receptor type-2A gene is associated with a worse response to a weight loss intervention in subjects with metabolic syndrome.

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