title: Enterovirus RNA in peripheral blood may be associated with the variants of rs1990760, a common type 1 diabetes associated polymorphism in IFIH1.
abstract: OBJECTIVE
  Polymorphisms in the IFIH1 (common rs1990760 and four rare rs35667974, rs35337543, rs35744605, rs35732034) have been convincingly associated with type 1 diabetes. The encoded protein (interferon-induced helicase C domain-containing protein 1) senses double-stranded RNA during replication of Picornavirales, including Enterovirus, a genus suspected in the etiology of type 1 diabetes. We therefore investigated whether the polymorphisms are associated with differences in the frequency of enterovirus RNA in blood.
  
  
  METHODS
  The study included 1001 blood samples, each from a child participating in the Norwegian 'Environmental Triggers of Type 1 Diabetes: the MIDIA study'. The enterovirus RNA was tested using qualitative semi-nested real-time reverse transcriptase PCR on RNA extracted from frozen cell packs after removal of plasma. Stool samples previously analyzed for enterovirus RNA were available in 417 children.
  
  
  RESULTS
  The genotypes of IFIH1 rs1990760 were associated with different frequencies of enterovirus RNA in blood (7.0%, 14.4% and 9.5% bloods were enterovirus positive among children carrying the Ala/Ala, Ala/Thr and Thr/Thr genotypes, respectively, p = 0.012). This association remained essentially unchanged after adjustment for age and calendar year. The presence of enterovirus in the concomitantly sampled stool further increased the likelihood of enterovirus RNA in blood (odds ratio 2.40, CI 95% 1.13-4.70), but did not affect the association with IFIH1 rs1990760. The rare polymorphisms (individually, or pooled) were not significantly associated with enterovirus RNA in blood.
  
  
  CONCLUSIONS
  The common IFIH1 SNP may modify the frequency of enterovirus RNA in blood of healthy children. This effect can help explain the association of IFIH1 with type 1 diabetes.
authors.affiliation: 2nd Faculty of Medicine, Department of Paediatrics, Charles University in Prague and University Hospital Motol, Prague, The Czech Republic. Ondrej.Cinek@Lfmotol.cuni.cz
authors.forename: Ondrej
authors.initials: O
authors.lastname: Cinek
authors.forename: German
authors.initials: G
authors.lastname: Tapia
authors.forename: Elisabet
authors.initials: E
authors.lastname: Witsø
authors.forename: Lenka
authors.initials: L
authors.lastname: Kramna
authors.forename: Katerina
authors.initials: K
authors.lastname: Holkova
authors.forename: Trond
authors.initials: T
authors.lastname: Rasmussen
authors.forename: Lars C
authors.initials: LC
authors.lastname: Stene
authors.forename: Kjersti S
authors.initials: KS
authors.lastname: Rønningen
mesh_terms: D053487:DEAD-box RNA Helicases / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000821:virology*; D004770:Enterovirus / Q000235:genetics*; D005243:Feces / Q000821:virology; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D015999:Multivariate Analysis; D009664:Norway; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012367:RNA, Viral / Q000097:blood*
chemical_list: D012367:RNA, Viral; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1