title: Risk genes and autoantibodies in Egyptian children with type 1 diabetes - low frequency of autoantibodies in carriers of the HLA-DRB1*04:05-DQA1*03-DQB1*02 risk haplotype.
abstract: BACKGROUND
  The study aimed to define the frequencies of type 1 diabetes-associated gene polymorphisms and their associations with various diabetes-associated autoantibodies in Egyptian children.
  
  
  METHODS
  One hundred and one children with type 1 diabetes and 160 healthy controls from the same region were studied for HLA-DQB1, HLA-DQA1, and HLA-DRB1 (DR4 subtypes) alleles; for INS and protein tyrosine phosphatase, non-receptor type 22 gene polymorphisms (rs689 and rs2476601); and for diabetes-associated autoantibodies.
  
  
  RESULTS
  Most children with diabetes (77.2%) were positive for the HLA-(DR3)-DQA1*05-DQB1*02 (DR3-DQ2) haplotype compared with 26.2% of the controls (OR = 9.5; p < 0.001). HLA-DRB1*04:02-DQA1*03-DQB1*03:02 (DR4-DQ8) (26.7%, OR = 3.3; p < 0.001), DRB1*04:05-DQA1*03-DQB1*02 (DR4-DQ2) (23.8%, OR 5.2; p < 0.001), and DRB1*04:05-DQA1*03-DQB1*03:02 (DR4-DQ8) (8.9%, OR = 7.7; p = 0.007) were also significantly increased. HLA-(DR15)-DQB1*06:01, (DR13)-DQB1*06:03, and DRB1*04:03-DQA1*03-DQB1*03:02 were the most protective haplotypes with OR values from 0.04 to 0.06. Patients positive for DR3-DQ2 but negative for DR4 haplotypes had a high frequency of glutamic acid decarboxylase antibodies (78%; p < 0.001 versus other genotypes), but only 26.6% of those with DR3-DQ2/DR4-DQ2 tested positive for glutamic acid decarboxylase antibodies (p = 0.006 versus other genotypes). Subjects with the DR4-DQ8 haplotype without DR3-DQ2 or DR4-DQ2 were more often positive for islet antigen-2 and zinc transporter 8 antibodies (55.5%, p = 0.007 and 55.5%, p = 0.01 respectively). The AA genotype of the INS gene was more common in patients than in controls (75.2 versus 59.5%, OR = 2.07; p = 0.018).
  
  
  CONCLUSIONS
  Besides a strong HLA-DR3-DQ2 association, a relatively high frequency of the DR4-DQ2 haplotype characterized the diabetic population. The low frequency of autoantibodies in children with HLA-DR4-DQ2 may indicate specific pathogenetic pathways associated with this haplotype.
authors.affiliation: Immunogenetics Laboratory, University of Turku, Turku, Finland; Department of Microbiology and Immunology, Faculty of Medicine, South Valley University, Qena, Egypt.
authors.forename: Mostafa I
authors.initials: MI
authors.lastname: El-Amir
authors.forename: Mohamed Ali
authors.initials: MA
authors.lastname: El-Feky
authors.forename: Antti-Pekka
authors.initials: AP
authors.lastname: Laine
authors.forename: Taina
authors.initials: T
authors.lastname: Härkönen
authors.forename: Omnia
authors.initials: O
authors.lastname: El-Badawy
authors.forename: Azza A
authors.initials: AA
authors.lastname: Eltayeb
authors.forename: Tarek Taha
authors.initials: TT
authors.lastname: El-Melegy
authors.forename: Minna
authors.initials: M
authors.lastname: Kiviniemi
authors.forename: Mikael
authors.initials: M
authors.lastname: Knip
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059848:HLA-DQ alpha-Chains / Q000235:genetics* / Q000276:immunology; D059866:HLA-DQ beta-Chains / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D011379:Prognosis; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; C527195:HLA-DRB1*04 antigen; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: Egypt; HLA; INS; PTPN22; autoantibodies; type 1 diabetes