PMID- 30915320
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2296-2360 (Print)
IS  - 2296-2360 (Electronic)
IS  - 2296-2360 (Linking)
VI  - 7
DP  - 2019
TI  - Dual Role of PTPN22 but Not NLRP3 Inflammasome Polymorphisms in Type 1 Diabetes 
      and Celiac Disease in Children.
PG  - 63
LID - 10.3389/fped.2019.00063 [doi]
LID - 63
AB  - Genetic polymorphisms in genes coding for inflammasome components 
      nucleotide-binding oligomerization domain leucine rich repeat and pyrin 
      domain-containing protein 3 (NLRP3) and caspase recruitment domain-containing 
      protein 8 (CARD8) have been associated with autoinflammatory and autoimmune 
      diseases. On the other hand several studies suggested that NLRP3 inflammasome 
      contributes to maintenance of gastrointestinal immune homeostasis and that 
      activation of NLRP3 is regulated by protein tyrosine phosphatase non-receptor 22 
      (PTPN22). PTPN22 polymorphism was implicated in the risk for various autoimmune 
      diseases including type 1 diabetes (T1D) but not for celiac disease (CD). The aim 
      of our study was to evaluate the role of inflammasome related polymorphisms in 
      subjects with either T1D or CD as well as in subjects affected by both diseases. 
      We examined PTPN22 rs2476601 (p.Arg620Trp), NLRP3 rs35829419 (p.Gln705Lys), and 
      CARD8 rs2043211 (p.Cys10Ter) in 66 subjects with coexisting T1D and CD, 65 
      subjects with T1D who did not develop CD, 67 subjects diagnosed only with CD and 
      127 healthy unrelated Slovenian individuals. All results were adjusted for 
      clinical characteristic and human leukocyte antigen (HLA) risk. PTPN22 rs2476601 
      allele was significantly more frequent among subjects with T1D (P(adj) = 0.001) 
      and less frequent in subjects with CD (P(adj) = 0.039) when compared to controls. 
      In patients with coexisting T1D and CD this variant was significantly less 
      frequent compared to T1D group (P(adj) = 0.010). Protective effect on CD 
      development in individuals with T1D was observed only within the low risk HLA 
      group. On the other hand, we found no association of NLRP3 rs35829419 and CARD8 
      rs2043211 with the development of T1D, CD or both diseases together. In 
      conclusion PTPN22 rs2476601polymorphism was significantly associated with the 
      risk of developing T1D in Slovenian population, while no associations of 
      proinflammatory NLRP3 and CARD8 polymorphisms with T1D and CD were observed. 
      Interestingly, the same PTPN22 variant protected from CD. We hypothesize that 
      this effect may be mediated through the NLRP3 inflammasome activation.
FAU - Smigoc Schweiger, Darja
AU  - Smigoc Schweiger D
AD  - Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, 
      University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, 
      Slovenia.
FAU - Goricar, Katja
AU  - Goricar K
AD  - Pharmacogenetics Laboratory, Faculty of Medicine, Institute of Biochemistry, 
      University of Ljubljana, Ljubljana, Slovenia.
FAU - Hovnik, Tinka
AU  - Hovnik T
AD  - Unit of Special Laboratory Diagnostics, University Children's Hospital, 
      University Medical Centre Ljubljana, Ljubljana, Slovenia.
FAU - Mendez, Andrijana
AU  - Mendez A
AD  - Tissue Typing Centre, Blood Transfusion Center of Slovenia, Ljubljana, Slovenia.
FAU - Bratina, Natasa
AU  - Bratina N
AD  - Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, 
      University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, 
      Slovenia.
AD  - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
FAU - Brecelj, Jernej
AU  - Brecelj J
AD  - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
AD  - Department of Gastroenterology, Hepatology and Nutrition, University Children's 
      Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.
FAU - Vidan-Jeras, Blanka
AU  - Vidan-Jeras B
AD  - Tissue Typing Centre, Blood Transfusion Center of Slovenia, Ljubljana, Slovenia.
FAU - Battelino, Tadej
AU  - Battelino T
AD  - Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, 
      University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, 
      Slovenia.
AD  - Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
FAU - Dolzan, Vita
AU  - Dolzan V
AD  - Pharmacogenetics Laboratory, Faculty of Medicine, Institute of Biochemistry, 
      University of Ljubljana, Ljubljana, Slovenia.
LA  - eng
PT  - Journal Article
DEP - 20190312
PL  - Switzerland
TA  - Front Pediatr
JT  - Frontiers in pediatrics
JID - 101615492
PMC - PMC6422865
OTO - NOTNLM
OT  - CARD8
OT  - NLRP3
OT  - PTPN22
OT  - celiac disease
OT  - inflammasome
OT  - type 1 diabetes
EDAT- 2019/03/28 06:00
MHDA- 2019/03/28 06:01
PMCR- 2019/03/12
CRDT- 2019/03/28 06:00
PHST- 2018/11/07 00:00 [received]
PHST- 2019/02/18 00:00 [accepted]
PHST- 2019/03/28 06:00 [entrez]
PHST- 2019/03/28 06:00 [pubmed]
PHST- 2019/03/28 06:01 [medline]
PHST- 2019/03/12 00:00 [pmc-release]
AID - 10.3389/fped.2019.00063 [doi]
PST - epublish
SO  - Front Pediatr. 2019 Mar 12;7:63. doi: 10.3389/fped.2019.00063. eCollection 2019.