Sequence variation within the major histocompatibility complex subregion centromeric of HLA class II in type 1 diabetes
| Autor: | Bart O. Roep, P. Eerligh, A. R. Van Der Slik, B. P. C. Koeleman, I. Van Den Eng, Marius J. Giphart, Ilias I.N. Doxiadis |
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| Rok vydání: | 2007 |
| Předmět: |
Risk
Receptors Retinoic Acid Immunology Single-nucleotide polymorphism Retinoic acid receptor beta Major histocompatibility complex Biochemistry Calcitriol receptor Linkage Disequilibrium Major Histocompatibility Complex Gene Frequency HLA Antigens Genotype Genetics Humans Immunology and Allergy Genetic Predisposition to Disease Allele Gene Alleles biology Haplotype Histocompatibility Antigens Class II Genetic Variation nutritional and metabolic diseases Sequence Analysis DNA General Medicine Diabetes Mellitus Type 1 Haplotypes Case-Control Studies biology.protein |
| Zdroj: | Tissue Antigens. 69:348-353 |
| ISSN: | 1399-0039 0001-2815 |
| Popis: | The extended major histocompatibility complex (xMHC) has been studied intensively with regard to type 1 diabetes (T1D) predisposition. So far, little attention has been given to the subregion centromeric of MHC class II. We selected five single nucleotide polymorphisms in genes with potential immune-related functions in the genomic regions of death-domain-associated protein 6 (DAXX, apoptosis associated), TAP-binding protein (TAPBP, human leukocyte antigen class I loading) and retinoic acid receptor beta (RXRB, vitamin D receptor function) that may bear relevance to the pathogenesis of T1D. A total of 277 unrelated individuals with juvenile-onset T1D and 286 control subjects were genotyped using sequence-specific priming-polymerase chain reaction. The genotype and allelic frequencies of the markers tested were not significantly different between patients and control subjects. Subsequent haplotype analysis showed six DAXX-TAPBP-RXRB haplotypic configurations. No difference was observed between patients and control cohorts when stratified for T1D high-risk DQ2-DR17 and DQ8-DR4 haplotypes. However, the distribution of these haplotypes affected T1D susceptibility encoded by the intermediate risk haplotypes DQ5-DR1 and DQ2-DR7 by increasing and decreasing susceptibility, respectively. We propose that studying genetic variants in the xMHC may be particularly rewarding to define disease pathways in patients displaying intermediate risk DQ-DR haplotypes. |
| Databáze: | OpenAIRE |
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