title: The A allele of the rs1990760 polymorphism in the IFIH1 gene is associated with protection for arterial hypertension in type 1 diabetic patients and with expression of this gene in human mononuclear cells.
abstract: BACKGROUND
  The rs1990760 polymorphism of interferon induced with helicase C domain 1 (IFIH1) has been associated with type 1 diabetes mellitus (T1DM). Here, we investigated whether this polymorphism is associated with T1DM or its clinical characteristics in a Brazilian population, and if IFIH1 gene expression in mononuclear cells from T1DM patients differs according to the genotypes of this polymorphism. A meta-analysis was also conducted to evaluate if the rs1990760 polymorphism is associated with T1DM.
  
  
  METHODS
  Frequencies of the rs1990760 polymorphism were analyzed in 527 T1DM patients and in 517 healthy subjects. IFIH1 gene expressions according to genotypes were measured in a sub-sample of 26 T1DM patients by quantitative real-time PCR.
  
  
  RESULTS
  Our data show the association of the A allele with risk to T1DM under a dominant model of inheritance [odds ratio (OR) = 1.421, P = 0.037], adjusting for ethnicity. The meta-analysis revealed significant association between the rs199760A allele and risk for T1DM for all analyzed inheritance models. Surprisingly, T1DM patients carrying the A allele showed lower levels of systolic (P = 0.001) and diastolic (P = 1 × 10(-10)) blood pressures as compared to G/G carriers. Furthermore, the A/A genotype seems to be associated with protection to arterial hypertension (AH) after adjustment for covariates (OR = 0.339, P = 0.019). IFIH1 gene expression in mononuclear cells from 26 T1DM patients did not differ among genotypes (P = 0.274). Nevertheless, IFIH1 gene expression was increased in mononuclear cells from T1DM patients with AH as compared with T1DM patients without AH [6.7 (1.7-2.0) vs. 1.8 (1.3-7.1) arbitrary units; P = 0.036]. The association with blood pressures and AH was not observed in patients with type 2 diabetes mellitus.
  
  
  CONCLUSIONS
  Our results indicate that the rs1990760 polymorphism is associated with T1DM. Interestingly, the rs1990760 A allele seems to be associated with protection for AH in T1DM patients. Further studies are needed to confirm the association with AH.
authors.affiliation: Laboratory of Biology of Human Pancreatic Islet, Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil ; Postgraduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Bouças
authors.affiliation: Laboratory of Biology of Human Pancreatic Islet, Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil ; Postgraduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Letícia A
authors.initials: LA
authors.lastname: Brondani
authors.affiliation: Laboratory of Biology of Human Pancreatic Islet, Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil ; Postgraduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Bianca M
authors.initials: BM
authors.lastname: Souza
authors.affiliation: Postgraduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Natália E
authors.initials: NE
authors.lastname: Lemos
authors.affiliation: Laboratory of Biology of Human Pancreatic Islet, Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: de Oliveira
authors.affiliation: Postgraduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Luis H
authors.initials: LH
authors.lastname: Canani
authors.affiliation: Laboratory of Biology of Human Pancreatic Islet, Endocrinology Division, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil ; Postgraduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Daisy
authors.initials: D
authors.lastname: Crispim
mesh_terms: D000328:Adult; D000483:Alleles; D001794:Blood Pressure; D001938:Brazil; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000209:etiology* / Q000517:prevention & control; D000072640:Interferon-Induced Helicase, IFIH1; D007963:Leukocytes, Mononuclear; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic
chemical_list: C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1