Genetically dependent ERBB3 expression modulates antigen presenting cell function and type 1 diabetes risk.

Hdl Handle:
http://hdl.handle.net/10675.2/19
Title:
Genetically dependent ERBB3 expression modulates antigen presenting cell function and type 1 diabetes risk.
Authors:
Wang, Hongjie; Jin, Yulan; Reddy, M V Prasad Linga; Podolsky, Robert H.; Liu, Siyang; Yang, Ping; Bode, Bruce; Reed, John Chip; Steed, R. Dennis; Anderson, Stephen W.; Steed, Leigh; Hopkins, Diane; Huang, Yihua; She, Jin-Xiong
Abstract:
Type 1 diabetes (T1D) is an autoimmune disease resulting from the complex interaction between multiple susceptibility genes, environmental factors and the immune system. Over 40 T1D susceptibility regions have been suggested by recent genome-wide association studies; however, the specific genes and their role in the disease remain elusive. The objective of this study is to identify the susceptibility gene(s) in the 12q13 region and investigate the functional link to the disease pathogenesis. A total of 19 SNPs in the 12q13 region were analyzed by the TaqMan assay for 1,434 T1D patients and 1,865 controls. Thirteen of the SNPs are associated with T1D (best p = 4x10(-11)), thus providing confirmatory evidence for at least one susceptibility gene in this region. To identify candidate genes, expression of six genes in the region was analyzed by real-time RT-PCR for PBMCs from 192 T1D patients and 192 controls. SNP genotypes in the 12q13 region are the main factors that determine ERBB3 mRNA levels in PBMCs. The protective genotypes for T1D are associated with higher ERBB3 mRNA level (p<10(-10)). Furthermore, ERBB3 protein is expressed on the surface of CD11c(+) cells (dendritic cells and monocytes) in peripheral blood after stimulation with LPS, polyI:C or CpG. Subjects with protective genotypes have significantly higher percentages of ERBB3(+) monocytes and dendritic cells (p = 1.1x10(-9)); and the percentages of ERBB3(+) cells positively correlate with the ability of APC to stimulate T cell proliferation (R(2) = 0.90, p<0.0001). Our results indicate that ERBB3 plays a critical role in determining APC function and potentially T1D pathogenesis.
Citation:
PLoS One. 2010 Jul 26; 5(7):e11789
Issue Date:
29-Jul-2010
URI:
http://hdl.handle.net/10675.2/19
DOI:
10.1371/journal.pone.0011789
PubMed ID:
20668683
PubMed Central ID:
PMC2909911
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
ISSN:
1932-6203
Appears in Collections:
Center for Biotechnology and Genomic Medicine: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, Hongjieen_US
dc.contributor.authorJin, Yulanen_US
dc.contributor.authorReddy, M V Prasad Lingaen_US
dc.contributor.authorPodolsky, Robert H.en_US
dc.contributor.authorLiu, Siyangen_US
dc.contributor.authorYang, Pingen_US
dc.contributor.authorBode, Bruceen_US
dc.contributor.authorReed, John Chipen_US
dc.contributor.authorSteed, R. Dennisen_US
dc.contributor.authorAnderson, Stephen W.en_US
dc.contributor.authorSteed, Leighen_US
dc.contributor.authorHopkins, Dianeen_US
dc.contributor.authorHuang, Yihuaen_US
dc.contributor.authorShe, Jin-Xiongen_US
dc.date.accessioned2010-09-24T20:59:21Z-
dc.date.available2010-09-24T20:59:21Z-
dc.date.issued2010-07-29en_US
dc.identifier.citationPLoS One. 2010 Jul 26; 5(7):e11789en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid20668683en_US
dc.identifier.doi10.1371/journal.pone.0011789en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/19-
dc.description.abstractType 1 diabetes (T1D) is an autoimmune disease resulting from the complex interaction between multiple susceptibility genes, environmental factors and the immune system. Over 40 T1D susceptibility regions have been suggested by recent genome-wide association studies; however, the specific genes and their role in the disease remain elusive. The objective of this study is to identify the susceptibility gene(s) in the 12q13 region and investigate the functional link to the disease pathogenesis. A total of 19 SNPs in the 12q13 region were analyzed by the TaqMan assay for 1,434 T1D patients and 1,865 controls. Thirteen of the SNPs are associated with T1D (best p = 4x10(-11)), thus providing confirmatory evidence for at least one susceptibility gene in this region. To identify candidate genes, expression of six genes in the region was analyzed by real-time RT-PCR for PBMCs from 192 T1D patients and 192 controls. SNP genotypes in the 12q13 region are the main factors that determine ERBB3 mRNA levels in PBMCs. The protective genotypes for T1D are associated with higher ERBB3 mRNA level (p<10(-10)). Furthermore, ERBB3 protein is expressed on the surface of CD11c(+) cells (dendritic cells and monocytes) in peripheral blood after stimulation with LPS, polyI:C or CpG. Subjects with protective genotypes have significantly higher percentages of ERBB3(+) monocytes and dendritic cells (p = 1.1x10(-9)); and the percentages of ERBB3(+) cells positively correlate with the ability of APC to stimulate T cell proliferation (R(2) = 0.90, p<0.0001). Our results indicate that ERBB3 plays a critical role in determining APC function and potentially T1D pathogenesis.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.titleGenetically dependent ERBB3 expression modulates antigen presenting cell function and type 1 diabetes risk.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC2909911en_US
dc.contributor.corporatenameCenter for Biotechnology and Genomic Medicineen_US
dc.contributor.corporatenameDepartment of Medicineen_US
dc.contributor.corporatenameDepartment of Pathologyen_US

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