HLA class II associations in juvenile Graves' disease: indication of a strong protective role of the DRBl*0701, DQAl*0201 haplotype

Abstract

Previous studies have shown that HLA-DRB1*0301 and DQA1*0501 are associated with susceptibility to Graves' disease. Ninety Danish patients with early onset of Graves' disease and 102-192 controls were analyzed for HLA-DR and -DQ to investigate if the same associations exist in the juvenile form of Graves' disease. Both DRB1*0301 and DQA1*0501 were highly significantly increased in the patients with relative risks of 8.0 and 4.6, which are higher than those seen in adults. Stratification showed that DRB1*0301 is more strongly associated than DQA1*0501. Surprisingly, the DRB1*0701,DQA1*0201 haplotype was completely absent from this group of patients, indicating a strong protective role of this haplotype in juvenile Graves' disease.

HLA-DRB1108, DRB1103/DRB310101, and DRB310202 Are Susceptibility Genes for Graves’ Disease in North American Caucasians, Whereas DRB1107 Is Protective1

“…In addition, a study of Caucasian patients suggested that the relative risk for DRB1*0301 was higher for juvenile patients than for adult patients with Graves' disease observed in other studies (12). Also, the DRB1*0701, DQA1*0201 haplotype has been shown to be protective for the juvenile form of Graves' disease (12).…”

New HLA DRB1 and DQB1 Haplotypes in a Pedigree of Familial Graves' Disease in Japan

“…Positive associations were obtained with the haplotypes of DRB1*0803, DQB1*1403, DQA1*0103 alleles [32], DRB1*0803, DQA1*0103, DQB1*0601 alleles [32], DRB1*1403, DQA1*0501, DQB1*0301 alleles [32], DRB1*0405, DQB1*0401 alleles [13], and DPB1*0501 alleles [28,33]. Also, the positive association of different haplotypes with Graves' disease was reported in other ethnic population; that is, DQB1* 0301, DR 11 and DR 3 in male Caucasian patients [30], DRB3*0202, DQA1*0501 in adult African Americans [31], DRB1*0301, DRB1*0201, DRB3*0101 in juvenile Danish patients [25,26], and DQB1*0303 in child Chinese patients [24]. The frequency of hyperthyroidism among familial Graves' disease is 2.1-3.1% in Japan [35].…”

“…Both genetic and environmental factors may affect the development of Graves' disease. Such an autoimmune mechanism could be associated with HLA on chromosome 6p [5][6][7][8][9][10][11][12][13][24][25][26][27][28][29][30][31][32][33] and CTLA-4 on chromosome 2q33 [14][15][16][17][18]. There are several different results regarding HLA haplotypes associated with Graves' disease in Japan [13,28,29,32,33].…”

“…In the literature HLA typing has a strong association with the development of Graves' disease with childhood onset, but CTLA-4 polymorphism does not [13]. In addition, HLA polymorphism associated with Graves' disease is different between childhood and adult onset [5][6][7][8][9][10][11][12][13][24][25][26][27][28][29][30][31][32][33].…”

Association of CD40 and thyroglobulin genes with later-onset Graves' disease in Taiwanese patients

“…In addition, another study suggested that the relative risk for DRB1*0301 was higher for juvenile patients than for adult patients with GD in Caucasian patients (12). Therefore, we decided to investigate the relationship of age at onset of GD with CD40 and TG gene susceptibilities in a Taiwanese population.…”