Several autoimmune diseases are associated with the same human leukocyte antigen specificity. For example, insulin dependent diabetes mellitus, Graves' disease and Hashimoto's thyroiditis are associated with HLA-DR3. Analysis of HLA-DR and DQ
restriction fragment length polymorphisms indicate that the DQ subregion, which is linkage disequilibrium with DR loci, is more closely linked to the disease susceptibility genes. Recently associations with the HLA-DQA1 locus has been described.
Since no study on the HLA-DQA1 in autoimmune endocrine diseases has been done in Korea, this investigation was performed to demonstrate the pattern of HLA-DQA1 distribution in Korean Graves' disease, Hashimoto's thyroiditis and IDDM patients.
After amplification of exon 2 DQA1 gene with polymerase chain reaction (PCR) procedure, we used non-radioactive HLA-DQA1 allele specific oligonucleotide (ASO) probes which iabelled with horseradish peroxidase (HRP) conupled to the 5'end of the
oligouncleotide for the HLA-DQA1 typing.
@ES The results were as follows ;
@EN 1) The first domain of the DQA1 gene was amplified from minimum 1 ng of genomic DNA with use of the PCR. And from 1 ㎍ DNA samples, all the samples were successfully amplified which have a product of approximately 242 bp.
2) Only one specific probe was hybidized to each cell line, e.g. RH 83 probe to TAB(HLA-DQA1* 0103 homozygosity), GH 67 probe to DKB (HLA-DQA*0301 homozygosity) and GH 66 probe to LUY (HLA-DQA1*0601 homozygosity). According to these results, we
accruately determined HLA-DQA1 subtypes in study subjects.
3) Frequency of DQA1*0301 allele in Korean was high and DQA1*0201 allele was low compared to other populations.
4) In IDDM patients, DQA1*0301 allele was significantly increased (relative risk 6.6, p=0.03) compared with controls. However the frequencies of DQA1*0101, *0102, *0103 allele was decreased among patients (relative risk 0.28, p=0.02).
5) In Graves' disease and Hashimoto's thyroiditis, there was no statistically significant HLA-DQA1 alleles which was associated with disease susceptibility.
These results suggest that HLA-DQA1*0301 allele is positively associated with IDDM and HLA-DQA1*0101, *0102, *0103 allele is negatively associated with IDDM in Korean as in other populations. But in autoimmune thyroid disease, we can not find any
HLA-DQA1 associations. (J Kor Soc Endocrinol 7:320~330)
|