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Genetic variation in selenoprotein S influences inflammatory response

Curran, Joanne E., Jowett, Jeremy B. M., Elliott, Kate S., Gao, Yuan, Gluschenko, Kristi, Jianmin, Wang, Azim, Dalia M Abel, Cai, Guowen, Mahaney, Michael C., Comuzzie, Anothony G., Dyer, Thomas D., Walder, Ken, Zimmet, Paul, MacCluer, Jean W., Collier, Greg R., Kissebah, Ahmed H. and Blangero, John 2005, Genetic variation in selenoprotein S influences inflammatory response, Nature genetics, vol. 37, no. 11, pp. 1234-1241.

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Title Genetic variation in selenoprotein S influences inflammatory response
Author(s) Curran, Joanne E.
Jowett, Jeremy B. M.
Elliott, Kate S.
Gao, Yuan
Gluschenko, Kristi
Jianmin, Wang
Azim, Dalia M Abel
Cai, Guowen
Mahaney, Michael C.
Comuzzie, Anothony G.
Dyer, Thomas D.
Walder, Ken
Zimmet, Paul
MacCluer, Jean W.
Collier, Greg R.
Kissebah, Ahmed H.
Blangero, John
Journal name Nature genetics
Volume number 37
Issue number 11
Start page 1234
End page 1241
Publisher Nature Publishing Group
Place of publication New York, N.Y.
Publication date 2005-11
ISSN 0028-0836
1476-4687
Summary Chronic inflammation has a pathological role in many common diseases and is influenced by both genetic and environmental factors. Here we assess the role of genetic variation in selenoprotein S (SEPS1, also called SELS or SELENOS), a gene involved in stress response in the endoplasmic reticulum and inflammation control. After resequencing SEPS1, we genotyped 13 SNPs in 522 individuals from 92 families. As inflammation biomarkers, we measured plasma levels of IL-6, IL-1b and TNF-a. Bayesian quantitative trait nucleotide analysis identified associations between SEPS1 polymorphisms and all three proinflammatory
cytokines. One promoter variant, 105G-A, showed strong evidence for an association with each cytokine (multivariate P = 0.0000002). Functional analysis of this polymorphism showed that the A variant significantly impaired SEPS1 expression after exposure to endoplasmic reticulum stress agents (P = 0.00006). Furthermore, suppression of SEPS1 by short interfering RNA in macrophage cells increased the release of IL-6 and TNF-a. To investigate further the significance of the observed associations, we genotyped 105G-A in 419 Mexican American individuals from 23 families for replication. This analysis confirmed a significant
association with both TNF-a (P = 0.0049) and IL-1b (P = 0.0101). These results provide a direct mechanistic link between SEPS1 and the production of inflammatory cytokines and suggest that SEPS1 has a role in mediating inflammation.
Language eng
Field of Research 060412 Quantitative Genetics (incl Disease and Trait Mapping Genetics)
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2005, Nature Publishing Group
Persistent URL http://hdl.handle.net/10536/DRO/DU:30006596

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.