title: Association analysis of PTPN22, CTLA4 and IFIH1 genes with type 1 diabetes in Colombian families.
abstract: BACKGROUND
  Protein tyrosine phosphatase, non-receptor type 22 (lymphoid) (PTPN22), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and interferon induced with helicase C domain 1 (IFIH1) are among the confirmed type 1 diabetes (T1D) susceptibility genes in several populations. The aim of this study was to evaluate the role of PTPN22, CTLA4, and IFIH1 gene variants in the development of T1D in a Colombian population.
  
  
  METHODS
  Associations of PTPN22, CTLA4, and IFIH1 variants with T1D were investigated in a sample of 197 nuclear families, including 205 affected children, in the Colombian population. Three to four single nucleotide polymorphisms (SNPs) were analyzed per gene: rs2476600, rs2476601, rs1217418, and rs2488457 for PTPN22; rs1990760, rs3747517, and rs10930046 for IFIH1; and rs231775, rs3087243, and rs231779 for CTLA4. A transmission disequilibrium test was performed for the global sample, in addition to stratified analysis considering autoimmunity, age at onset, and parent of origin. Haplotypes per gene were also analyzed.
  
  
  RESULTS
  There was no significant transmission distortion for CTLA4. Conversely, SNPs rs10930046 (IFIH1) and rs2476601 (PTPN222) exhibited significant transmission distortion of the C and T alleles, respectively, from parents to affected children (odds ratio [OR] 0.57 and 1.83, respectively). In addition, decreased transmission of the C allele for rs10930046 occurred preferentially from mothers. Stratification analysis revealed that this association was maintained in individuals who were positive for autoantibodies and in those with an age of diagnosis <5 years.
  
  
  CONCLUSIONS
  The results show that IFIH1 and PTPN22 are associated with T1D in Colombian families.
authors.affiliation: Gene Mapping Group, University of Antioquia, Medellín, Colombia.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Rodríguez
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Alfaro
authors.forename: Vital
authors.initials: V
authors.lastname: Balthazar
authors.forename: Nicolás
authors.initials: N
authors.lastname: Pineda Trujillo
mesh_terms: D017668:Age of Onset; D000483:Alleles; D060908:CTLA-4 Antigen / Q000235:genetics*; D002648:Child; D003105:Colombia / Q000453:epidemiology; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22; C452815:IFIH1 protein, human; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1
keywords: Colombia; IFIH1; PTPN22; association study; type 1 diabetes; 关键词：相关性研究，哥伦比亚，IFIH1，PTPN22，1型糖尿病。