The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes

Yulan Jin, Ashok Kumar Sharma, Colleen M. Davis, Diane Hopkins, Xiaoxiao Wang, David G. Robertson, Bruce Bode, Stephen W. Anderson, John Chip Reed, R. Dennis Steed, Leigh Steed, Jin-Xiong She

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE-Our previous gene expression microarray studies identified a number of genes differentially expressed in patients with type 1 diabetes (T1D) and islet autoantibody-positive subjects. This study was designed to validate these gene expression changes in T1D patients and to identify gene expression changes in diabetes complications. RESEARCH DESIGH ANDMETHODS-We performed high-throughput real-time RTPCR to validate gene expression changes in peripheral blood mononuclear cells (PBMCs) from a large sample set of 928 T1D patients and 922 control subjects. RESULTS-Of the 18 genes analyzed here, eight genes (S100A8, S100A9, MNDA, SELL, TGFB1, PSMB3, CD74, and IL12A) had higher expression and three genes (GNLY, PSMA4, and SMAD7) had lower expression in T1D patients compared with control subjects, indicating that genes involved in inflammation, immune regulation, and antigen processing and presentation are significantly altered in PBMCs from T1D patients. Furthermore, one adhesion molecule (SELL) and three inflammatory genes mainly expressed by myeloid cells (S100A8, S100A9, and MNDA) were significantly higher in T1D patients with complications (odds ratio [OR] 1.3-2.6, adjusted P value = 0.005-10 -8), especially those patients with neuropathy (OR 4.8-7.9, adjusted P value < 0.005). CONCLUSIONS-These findings suggest that inflammatory mediators secreted mainly by myeloid cells are implicated in T1D and its complications.

Original languageEnglish (US)
Pages (from-to)2794-2802
Number of pages9
JournalDiabetes Care
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2013

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Type 1 Diabetes Mellitus
Gene Expression
Genes
Antigen Presentation
Myeloid Cells
Diabetes Complications
Blood Cells
Odds Ratio
Autoantibodies
Inflammation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes. / Jin, Yulan; Sharma, Ashok Kumar; Davis, Colleen M.; Hopkins, Diane; Wang, Xiaoxiao; Robertson, David G.; Bode, Bruce; Anderson, Stephen W.; Reed, John Chip; Steed, R. Dennis; Steed, Leigh; She, Jin-Xiong.

In: Diabetes Care, Vol. 36, No. 9, 01.09.2013, p. 2794-2802.

Research output: Contribution to journalArticle

Jin, Y, Sharma, AK, Davis, CM, Hopkins, D, Wang, X, Robertson, DG, Bode, B, Anderson, SW, Reed, JC, Steed, RD, Steed, L & She, J-X 2013, 'The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes', Diabetes Care, vol. 36, no. 9, pp. 2794-2802. https://doi.org/10.2337/dc12-1986
Jin, Yulan ; Sharma, Ashok Kumar ; Davis, Colleen M. ; Hopkins, Diane ; Wang, Xiaoxiao ; Robertson, David G. ; Bode, Bruce ; Anderson, Stephen W. ; Reed, John Chip ; Steed, R. Dennis ; Steed, Leigh ; She, Jin-Xiong. / The expression of inflammatory genes is upregulated in peripheral blood of patients with type 1 diabetes. In: Diabetes Care. 2013 ; Vol. 36, No. 9. pp. 2794-2802.
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AU - Robertson, David G.

AU - Bode, Bruce

AU - Anderson, Stephen W.

AU - Reed, John Chip

AU - Steed, R. Dennis

AU - Steed, Leigh

AU - She, Jin-Xiong

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N2 - OBJECTIVE-Our previous gene expression microarray studies identified a number of genes differentially expressed in patients with type 1 diabetes (T1D) and islet autoantibody-positive subjects. This study was designed to validate these gene expression changes in T1D patients and to identify gene expression changes in diabetes complications. RESEARCH DESIGH ANDMETHODS-We performed high-throughput real-time RTPCR to validate gene expression changes in peripheral blood mononuclear cells (PBMCs) from a large sample set of 928 T1D patients and 922 control subjects. RESULTS-Of the 18 genes analyzed here, eight genes (S100A8, S100A9, MNDA, SELL, TGFB1, PSMB3, CD74, and IL12A) had higher expression and three genes (GNLY, PSMA4, and SMAD7) had lower expression in T1D patients compared with control subjects, indicating that genes involved in inflammation, immune regulation, and antigen processing and presentation are significantly altered in PBMCs from T1D patients. Furthermore, one adhesion molecule (SELL) and three inflammatory genes mainly expressed by myeloid cells (S100A8, S100A9, and MNDA) were significantly higher in T1D patients with complications (odds ratio [OR] 1.3-2.6, adjusted P value = 0.005-10 -8), especially those patients with neuropathy (OR 4.8-7.9, adjusted P value < 0.005). CONCLUSIONS-These findings suggest that inflammatory mediators secreted mainly by myeloid cells are implicated in T1D and its complications.

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