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: 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.
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Authors | Mostafa I El-Amir, Mohamed Ali El-Feky, Antti-Pekka Laine, Taina Härkönen, Omnia El-Badawy, Azza A Eltayeb, Tarek Taha El-Melegy, Minna Kiviniemi, Mikael Knip, Jorma Ilonen |
Journal | Diabetes/metabolism research and reviews
(Diabetes Metab Res Rev)
Vol. 31
Issue 3
Pg. 287-94
(Mar 2015)
ISSN: 1520-7560 [Electronic] England |
PMID | 25256132
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2014 John Wiley & Sons, Ltd. |
Chemical References |
- Autoantibodies
- HLA-DQ alpha-Chains
- HLA-DQ beta-Chains
- HLA-DQA1 antigen
- HLA-DQB1 antigen
- HLA-DRB1 Chains
- HLA-DRB1*04 antigen
- PTPN22 protein, human
- Protein Tyrosine Phosphatase, Non-Receptor Type 22
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Topics |
- Adolescent
- Alleles
- Autoantibodies
(blood, immunology)
- Case-Control Studies
- Child
- Child, Preschool
- Diabetes Mellitus, Type 1
(blood, genetics, immunology)
- Female
- Genetic Predisposition to Disease
- Genotype
- HLA-DQ alpha-Chains
(genetics, immunology)
- HLA-DQ beta-Chains
(genetics, immunology)
- HLA-DRB1 Chains
(genetics, immunology)
- Haplotypes
(genetics)
- Heterozygote
- Humans
- Infant
- Male
- Prognosis
- Protein Tyrosine Phosphatase, Non-Receptor Type 22
(genetics, immunology)
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