The nutrigenetic influence of the interaction between dietary vitamin E and TXN and COMT gene polymorphisms on waist circumference: a case control study.

Maria L Mansego,Sonsoles Morcillo,Carmen Ivorra,Gemma Rojo-Martínez,Verónica González-Albert,Josep Redon,Fernando Martinez,Juan C Martín-Escudero,Raúl Lopez-Izquierdo,F Javier Chaves,Federico Soriguer,Griselda De Marco

doi:10.1186/s12967-015-0652-4

Abstract

BackgroundAbdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population.MethodsA total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays.ResultsThe AO group had higher 8-Oxo-2′-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression.ConclusionsWC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0652-4) contains supplementary material, which is available to authorized users.

Highlights

Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS)
Participants allocated to the AO group had a higher BMI, waist circumference (WC), and hip and waist-hip ratio (WHR) than the non-AO group
The fact that heat shock factor 2 (HSF2) can only bind to this reverse region [gtcctgacctcctGAAGtctcagtg] when the c.-793C allele is present indicates the functionality of this polymorphism, and importantly, the differences in TXN transcription we describe between groups may be explained by the reduced ability that TT carriers have to produce normal levels of TXN mRNA

Summary

Introduction

Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The impact of increased quantities of reactive oxygen species (ROS) on several cellular systems in patients with AO has recently been described as a contributing factor to systemic OS and to the overall fat storage pattern [10]. ROS in adipocyte cells produce alterations in the endoplasmic reticulum which increases the proportion of unfolded or misfolded proteins and cellular stress [11]. They allow long-chain fatty acids bound to coenzyme A to accumulate, which lowers mitochondrial activity and encourages fat storage. OS increases insulin resistance which further contributes to fat accumulation in muscle, liver, and adipose tissue [12]

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