PMID- 24205307
OWN - NLM
STAT- MEDLINE
DCOM- 20140807
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 10
DP  - 2013
TI  - Influence of Atg5 mutation in SLE depends on functional IL-10 genotype.
PG  - e78756
LID - 10.1371/journal.pone.0078756 [doi]
LID - e78756
AB  - Increasing evidence supports the involvement of autophagy in the etiopathology of 
      autoimmune diseases. Despite the identification of autophagy-related protein 
      (Atg)-5 as one of the susceptibility loci in systemic Lupus erythematosus (SLE), 
      the consequences of the carriage of these mutations for patients remain unclear. 
      The present work analyzed the association of Atg5 rs573775 single nucleotide 
      polymorphism (SNP) with SLE susceptibility, IFNalpha, TNFalpha and IL-10 serum levels, 
      and clinical features, in 115 patients and 170 healthy individuals. Patients who 
      where carriers of the rs573775 T* minor allele presented lower IFNalpha levels than 
      those with the wild genotype, whereas the opposite result was detected for IL-10. 
      Thus, since IL-10 production was regulated by rs1800896 polymorphisms, we 
      evaluated the effect of this Atg5 mutation in genetically high and low IL-10 
      producers. Interestingly, we found that the rs573775 T* allele was a risk factor 
      for SLE in carriers of the high IL-10 producer genotype, but not among 
      genetically low producers. Moreover, IL-10 genotype influences SLE features in 
      patients presenting the Atg5 mutated allele. Specifically, carriage of the 
      rs573775 T* allele led to IL-10 upregulation, reduced IFNalpha and TNFalpha production 
      and a low frequency of cytopenia in patients with the high IL-10 producer 
      genotype, whereas patients with the same Atg5 allele that were low IL-10 
      producers presented reduced amounts of all these cytokines, had a lower 
      prevalence of anti-dsDNA antibodies and the latest onset age. In conclusion, the 
      Atg5 rs573775 T* allele seems to influence SLE susceptibility, cytokine 
      production and disease features depending on other factors such as functional 
      IL-10 genotype.
FAU - Lopez, Patricia
AU  - Lopez P
AD  - Department of Functional Biology, Immunology Area, Faculty of Medicine, 
      University of Oviedo, Oviedo, Spain.
FAU - Alonso-Perez, Elisa
AU  - Alonso-Perez E
FAU - Rodriguez-Carrio, Javier
AU  - Rodriguez-Carrio J
FAU - Suarez, Ana
AU  - Suarez A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131018
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (ATG5 protein, human)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (Interferon-alpha)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Adult
MH  - Alleles
MH  - Autophagy-Related Protein 5
MH  - Cohort Studies
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - *Genotype
MH  - Humans
MH  - Interferon-alpha/blood
MH  - Interleukin-10/*genetics
MH  - Lupus Erythematosus, Systemic/blood/*genetics
MH  - Male
MH  - Microtubule-Associated Proteins/*genetics
MH  - *Mutation
MH  - Polymorphism, Single Nucleotide
PMC - PMC3799636
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/11/10 06:00
MHDA- 2014/08/08 06:00
PMCR- 2013/10/18
CRDT- 2013/11/09 06:00
PHST- 2013/07/03 00:00 [received]
PHST- 2013/09/23 00:00 [accepted]
PHST- 2013/11/09 06:00 [entrez]
PHST- 2013/11/10 06:00 [pubmed]
PHST- 2014/08/08 06:00 [medline]
PHST- 2013/10/18 00:00 [pmc-release]
AID - PONE-D-13-27458 [pii]
AID - 10.1371/journal.pone.0078756 [doi]
PST - epublish
SO  - PLoS One. 2013 Oct 18;8(10):e78756. doi: 10.1371/journal.pone.0078756. 
      eCollection 2013.