PMID- 23925433
OWN - NLM
STAT- MEDLINE
DCOM- 20140325
LR  - 20211021
IS  - 1539-0829 (Electronic)
IS  - 1534-4827 (Linking)
VI  - 13
IP  - 5
DP  - 2013 Oct
TI  - Candidate genes expressed in human islets and their role in the pathogenesis of 
      type 1 diabetes.
PG  - 633-41
LID - 10.1007/s11892-013-0408-6 [doi]
AB  - In type 1 diabetes (T1D), the insulin-producing beta cells are destroyed by an 
      immune-mediated process leading to complete insulin deficiency. There is a strong 
      genetic component in T1D. Genes located in the human leukocyte antigen (HLA) 
      region are the most important genetic determinants of disease, but more than 40 
      additional loci are known to significantly affect T1D risk. Since most of the 
      currently known genetic candidates have annotated immune cell functions, it is 
      generally considered that most of the genetic susceptibility in T1D is caused by 
      variation in genes affecting immune cell function. Recent studies, however, 
      indicate that most T1D candidate genes are expressed in human islets suggesting 
      that the functions of the genes are not restricted to immune cells, but also play 
      roles in the islets and possibly the beta cells. Several candidates change 
      expression levels within the islets following exposure to proinflammatory 
      cytokines highlighting that these genes may be involved in the response of beta 
      cells to immune attack. In this review, the compiling evidence that many of the 
      candidate genes are expressed in islets and beta cells will be presented. Further, 
      we perform the first systematic human islet expression analysis of all genes 
      located in 50 T1D-associated GWAS loci using a published RNA sequencing dataset. 
      We find that 336 out of 857 genes are expressed in human islets and that many of 
      these interact in protein networks. Finally, the potential pathogenetic roles of 
      some candidate genes will be discussed.
FAU - Storling, Joachim
AU  - Storling J
AD  - Copenhagen Diabetes Research Center, Department of Paediatrics, Herlev University 
      Hospital, Herlev Ringvej, DK-2730, Herlev, Denmark, joachim.stoerling@regionh.dk.
FAU - Brorsson, Caroline Anna
AU  - Brorsson CA
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Curr Diab Rep
JT  - Current diabetes reports
JID - 101093791
SB  - IM
MH  - Diabetes Mellitus, Type 1/*genetics/pathology
MH  - *Gene Expression Regulation
MH  - *Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Islets of Langerhans/*metabolism/pathology
MH  - Reproducibility of Results
EDAT- 2013/08/09 06:00
MHDA- 2014/03/26 06:00
CRDT- 2013/08/09 06:00
PHST- 2013/08/09 06:00 [entrez]
PHST- 2013/08/09 06:00 [pubmed]
PHST- 2014/03/26 06:00 [medline]
AID - 10.1007/s11892-013-0408-6 [doi]
PST - ppublish
SO  - Curr Diab Rep. 2013 Oct;13(5):633-41. doi: 10.1007/s11892-013-0408-6.