Genetic variation in selenoprotein S influences inflammatory response

Curran, Joanne E.; Jowett, Jeremy B. M.; Elliott, Kate; Gao, Yuan; Gluschenko, K.; Wang, Jianmin; Azim, Dalia M Abel; Cai, Guowen; Mahaney, Michael C.; Comuzzie, Anthony G.; Dyer, Thomas D.; Walder, Ken; Zimmet, Paul; MacCluer, Jean W.; Collier, Greg R.; Kissebah, Ahmed H.; Blangero, John

doi:10.1038/ng1655

Cited by 340 publications

(303 citation statements)

References 32 publications

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“…Variations in the SEPS1 gene are associated with the circulating levels of inflammatory cytokines IL-1b, IL-6 and TNF-a. 34 A recent study conducted in two independent Finnish cohorts indicated that variation in the SEPS1 locus may have an effect on cardiovascular disease morbidity, especially in females. 35 Our results seem to suggest the involvement of SEPS1 as host factor that might be also involved in determining the individual susceptibility to AgP.…”

Section: Resultsmentioning

confidence: 99%

Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

et al. 2011

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Aggressive periodontitis (AgP) is a multifactorial disease. The distinctive aspect of periodontitis is that this disease must deal with a large number of genes interacting with one another and forming complex networks. Thus, it is reasonable to expect that gene-gene interaction may have a crucial role. Therefore, we carried out a pilot case-control study to identify the association of candidate epistatic interactions between genetic risk factors and susceptibility to AgP, by using both conventional parametric analyses and a higher order interactions model, based on the nonparametric Multifactor Dimensionality Reduction algorithm. We analyzed 122 AgP patients and 246 appropriate periodontally healthy individuals, and genotyped 28 polymorphisms, located within 14 candidate genes, chosen among the principal genetic variants pointed out from literature and having a role in inflammation and immunity. Our analyses provided significant evidence for gene-gene interactions in the development of AgP, in particular, present results: (a) indicate a possible role of two new polymorphisms, within SEPS1 and TNFRSF1B genes, in determining host individual susceptibility to AgP; (b) confirm the potential association between of IL-6 and Fc g-receptor polymorphisms and the disease; (c) exclude an essential contribution of IL-1 cluster gene polymorphisms to AgP in our Caucasian-Italian population.

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Section: Resultsmentioning

confidence: 99%

Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

et al. 2011

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“…200 A particular polymorphism of SelS was proven to be responsible for increased plasma level of the inflammatory cytokines. 201 A possible increased risk of several inflammatory diseases could be the consequence, but a direct correlation with stroke, autoimmune disorders or inflammatory bowel disease is still not proven. 188 As a whole, Se participates in the immune response through several actions: it regulates the balance of activity in the eicosanoid synthesis pathways, leading to preferential synthesis of leukotrienes and prostacyclins over thromboxanes and prostaglandins, and down-regulates cytokine and adhesion molecule expression.…”

Section: Immune Defence and Inflammatory Disordersmentioning

confidence: 99%

Selenium biochemistry and its role for human health

Roman¹,

Jitaru²,

Barbante³

2014

Metallomics

597

416

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Despite its very low level in humans, selenium plays an important and unique role among the (semi)metal trace essential elements because it is the only one for which incorporation into proteins is genetically encoded, as the constitutive part of the 21st amino acid, selenocysteine. Twenty-five selenoproteins have been identified so far in the human proteome. The biological functions of some of them are still unknown, whereas for others there is evidence for a role in antioxidant defence, redox state regulation and a wide variety of specific metabolic pathways. In relation to these functions, the selenoproteins emerged in recent years as possible biomarkers of several diseases such as diabetes and several forms of cancer. Comprehension of the selenium biochemical pathways under normal physiological conditions is therefore an important requisite to elucidate its preventing/therapeutic effect for human diseases. This review summarizes the most recent findings on the biochemistry of active selenium species in humans, and addresses the latest evidence on the link between selenium intake, selenoproteins functionality and beneficial health effects. Primary emphasis is given to the interpretation of biochemical mechanisms rather than epidemiological/observational data. In this context, the review includes the following sections: (1) brief introduction; (2) general nutritional aspects of selenium; (3) global view of selenium metabolic routes; (4) detailed characterization of all human selenoproteins; (5) detailed discussion of the relation between selenoproteins and a variety of human diseases.

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“…Reporter gene experiments indicate that the SNP have functional consequences. Second, SelS is another selenoprotein recently found to have a function in the ER stress response (33)(34)(35) . An SNP in the SELS promoter at position -105 is regarded as being functionally significant as it modulates levels of inflammatory markers such as TNF-a and interleukin (33) .…”

Section: Functional Single-nucleotide Polymorphisms In Sels and Othermentioning

confidence: 99%

“…Second, SelS is another selenoprotein recently found to have a function in the ER stress response (33)(34)(35) . An SNP in the SELS promoter at position -105 is regarded as being functionally significant as it modulates levels of inflammatory markers such as TNF-a and interleukin (33) . Third, SNP have been identified in the promoter region of the GPX3 gene coding for the plasma glutathione peroxidase GPx3 and gene reporter experiments suggest that these affect promoter activity (36,37) .…”

Section: Functional Single-nucleotide Polymorphisms In Sels and Othermentioning

confidence: 99%

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

Hesketh

Méplan

2011

Proc. Nutr. Soc.

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Micronutrients are essential for optimal human health. However, in some cases, raising intake by supplementation has not proven to be beneficial and there is even some evidence that supplementation may increase disease risk, highlighting the importance of assessing the functional status of micronutrients. Techniques such as gene microarrays and single-nucleotide polymorphism analysis have the potential to examine effects of micronutrient intake on patterns of gene expression and inter-individual variation in micronutrient metabolism. Recent genomic research related to selenium (Se) provides examples illustrating how studies of functional single-nucleotide polymorphism and gene expression patterns can reveal novel biomarkers of micronutrient function. Both in vitro and in vivo experiments show that there are functionally relevant polymorphisms in genes encoding glutathione peroxidases 1, 3 and 4, selenoprotein P, selenoprotein S and the 15 kDa selenoprotein. Disease association studies investigating these gene variants have so far been relatively small but an association of a polymorphism in the selenoprotein S gene with colorectal cancer risk has been replicated in two distinct populations. Future disease association studies should examine effects of multiple variants in combination with nutritional status. Gene microarray studies indicate that changes in Se intake alter expression of components of inflammatory, stress response and translation pathways. Our hypothesis is that Se intake and genetic factors have linked effects on stress response, inflammation and apoptotic pathways. Combining such data in a systems biology approach has the potential to identify both biomarkers of micronutrients status and sub-group populations at particular risk.

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Genetic variation in selenoprotein S influences inflammatory response

Cited by 340 publications

References 32 publications

Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

Gene–gene interaction among cytokine polymorphisms influence susceptibility to aggressive periodontitis

Selenium biochemistry and its role for human health

Transcriptomics and functional genetic polymorphisms as biomarkers of micronutrient function: focus on selenium as an exemplar

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