Some dietary factors can modulate the effect of the zinc transporters 8 polymorphism on the risk of metabolic syndrome

Hosseini-Esfahani, Firoozeh; Mirmiran, Parvin; Koochakpoor, Gelareh; Daneshpour, Maryam S.; Guity, Kamran; Azizi, Fereidoun

doi:10.1038/s41598-017-01762-9

Cited by 13 publications

(15 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This increased granular zinc uptake may deplete cytosolic zinc and affect β‐cell function. If so, it may need to be ameliorated with a higher dietary zinc intake .…”

Section: Discussionmentioning

confidence: 99%

The C‐terminal cytosolic domain of the human zinc transporter ZnT8 and its diabetes risk variant

2018

View full text Add to dashboard Cite

A significant aspect of the control of cellular zinc in eukarya is its subcellular re‐distribution. One of the four human vesicular zinc transporters, ZnT8, supplies the millimolar zinc concentrations of insulin granules in pancreatic β‐cells, affecting insulin processing, crystallisation and secretion. ZnT8 has a transmembrane and a C‐terminal cytosolic domain; the latter has important functions and purportedly mediates protein–protein interactions, senses cytosolic zinc and/or channels zinc to the transport site in the transmembrane domain (TMD). A common variant W325R in the C‐terminal domain (CTD) increases the risk to develop type 2 diabetes and affects autoantibody specificity in type 1 diabetes. To investigate the differences between the two protein variants, we purified and biophysically characterised both variants of the ZnT8 CTD [R325 variant of ZnT8 CTD (aa267–369) (ZnT8cR) and W325 variant of ZnT8 CTD (aa267–369) (ZnT8cW)]. The domains fold independently of the TMD. Remarkably, the ZnT8cW variant (diabetes protection in the full‐length protein) is less thermostable than the ZnT8cR variant (diabetes risk in the full‐length protein). The ZnT8cW monomers associate with higher affinity. Both CTD variants bind zinc with a stoichiometry that differs from bacterial homologues, emphasising the limitation of the latter as models for the structure and function of the human proteins. The relatively small but reproducible differences between the two ZnT8 CTD variants begin to provide a molecular basis for the different diabetes susceptibility caused by the full‐length ZnT8 proteins.

show abstract

“…This increased granular zinc uptake may deplete cytosolic zinc and affect β‐cell function. If so, it may need to be ameliorated with a higher dietary zinc intake .…”

Section: Discussionmentioning

confidence: 99%

The C‐terminal cytosolic domain of the human zinc transporter ZnT8 and its diabetes risk variant

2018

View full text Add to dashboard Cite

show abstract

“…Recently, studies aimed to delineate the effect of dietary factor interactions with ZnT8 polymorphism (rs13266634) and the risk of developing metabolic syndrome found a significant interaction among omega-3 fatty acid consumption and ZnT8 in the context of metabolic syndrome, dyslipidemia, and abdominal obesity [ 71 ]. Participants with the CC genotype benefited more from the consumption of omega-3 fatty acids than carriers of the CT + TT genotypes.…”

Section: Introductionmentioning

confidence: 99%

Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

et al. 2017

View full text Add to dashboard Cite

BackgroundZinc is a metal ion that is essential for growth and development, immunity, and metabolism, and therefore vital for life. Recent studies have highlighted zinc’s dynamic role as an insulin mimetic and a cellular second messenger that controls many processes associated with insulin signaling and other downstream pathways that are amendable to glycemic control.Main bodyMechanisms that contribute to the decompartmentalization of zinc and dysfunctional zinc transporter mechanisms, including zinc signaling are associated with metabolic disease, including type 2 diabetes. The actions of the proteins involved in the uptake, storage, compartmentalization and distribution of zinc in cells is under intense investigation. Of these, emerging research has highlighted a role for several zinc transporters in the initiation of zinc signaling events in cells that lead to metabolic processes associated with maintaining insulin sensitivity and thus glycemic homeostasis.ConclusionThis raises the possibility that zinc transporters could provide novel utility to be targeted experimentally and in a clinical setting to treat patients with insulin resistance and thus introduce a new class of drug target with utility for diabetes pharmacotherapy.

show abstract

“…Gene–diet interactions may play an important role in the inter-individual diversity observed in plasma lipid concentrations and consequently on CVD risk [ 7 – 9 ]. Genetic susceptibility to dyslipidemia may modulate the association of dietary intake and metabolic syndrome [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Genetic variations of cholesteryl ester transfer protein and diet interactions in relation to lipid profiles and coronary heart disease: a systematic review

et al. 2017

Self Cite

View full text Add to dashboard Cite

Data on diet–genotype interactions in the prevention or treatment of dyslipidemia have increased remarkably. This systematic review aimed to assess nutrigenetic studies regarding the modulating effect of diet on cholesteryl ester transfer protein (CETP) polymorphisms in relation to metabolic traits.Data were collected through studies published between 2000 and SEP. 2016 using five electronic databases. The quality of eligible studies was assessed using a 12-item quality checklist, derived from the STrengthening the REporting of Genetic Association Studies (STREGA) statement. CETP variants that had associations with lipid profiles in previous studies were extracted for drawing of the linkage disequilibrium (LD) plot.Among CETP variants, the rs9989419 best represented this genome wide association signal across all populations, based on LD r2 estimates from 1000 genomes references. In the 23 found eligible studies (clinical trials and observational), the TaqIB and I405V polymorphisms were the two most intensively studied. Two studies reported the effect of interaction between rs3764261 and diet on lipid levels. Regarding the rs708272 (Taq1B), individuals with the B1 risk allele showed better responses to dietary interventions than those with B2B2 genotype, whereas with I405V, inconsistent results have been reported. Modest alcohol consumption was associated with decreased risk of coronary heart disease among B2 carriers of rs708272.It is concluded that variations in the CETP gene may modulate the effects of dietary components on metabolic traits. These results have been controversial, indicating complex polygenic factors in metabolic response to diet and lack of uniformity in the study conditions and designs.Electronic supplementary materialThe online version of this article (10.1186/s12986-017-0231-1) contains supplementary material, which is available to authorized users.

show abstract

Some dietary factors can modulate the effect of the zinc transporters 8 polymorphism on the risk of metabolic syndrome

Cited by 13 publications

References 39 publications

The C‐terminal cytosolic domain of the human zinc transporter ZnT8 and its diabetes risk variant

The C‐terminal cytosolic domain of the human zinc transporter ZnT8 and its diabetes risk variant

Zinc transporters and insulin resistance: therapeutic implications for type 2 diabetes and metabolic disease

Genetic variations of cholesteryl ester transfer protein and diet interactions in relation to lipid profiles and coronary heart disease: a systematic review

Contact Info

Product

Resources

About