The Human Leukocyte Antigen HLA DRB3∗0202/DQA1∗0501 Haplotype Is Associated with Graves’ Disease in African Americans

Abstract

Information on genetic susceptibility to Graves' disease in African Americans is limited. We studied DRB1, DQB1, DRB3 subtypes, DQA1*0501, DQA1*0201, and CTLA-4 polymorphisms in 49 African American patients with adult onset Graves' disease and 47 racially-matched controls using PCR-based sequence-specific priming methods. There were no significant differences in DRB1 or DQB1 allelic frequencies or CTLA-4 polymorphisms between patients and controls. However, we found that the frequency of DRB3 was significantly increased in the patients (75.5% vs. 57.4%, P = 0.006, X2 = 3.52), especially for the DRB3*0202 subtype (53.1% vs. 23.4, P = 0.003, X2 = 8.91). In this one respect, the finding was in concordance with our previous observations in Caucasian patients with adult-onset Graves' disease. In addition, whereas the frequency of DQA1*0501 was increased (P = 0.018, X2 = 5.63) in our patients, the haplotype of DRB3/DQA1*0501, or DRB3*0202/DQA1*0501 was found to be more strongly associated (P = 0.008, X2 = 7.0; P = 0.0008, X2 = 11.34, respectively). These data suggest that DRB3*0202, particularly when found with DQA1*0501 in a haplotype is a susceptible gene(s) for Graves' disease in adult African Americans. Considering these data with those in Caucasian patients, our results would suggest that the primary Graves susceptible locus is likely DRB3 and not DRB1.

Genetics of autoimmune thyroid disease in the Lebanese population

“…For GD, we observed weak association with HLA DQB1*0302. In agreement with other studies, no association was found between HLA DQB1*0201 and HLA DQB1*0303 and GD (Zamani et al 2000;Chen et al 2000) ( Table 1 in the "Appendix"). Also, weak association was found between GD and DQB1*0302-DQA1*0501 haplotype, where the confidence interval was barely greater than one (P00.042, OR01.870, CI01.018-3.433).…”

“…Taken together, these data suggest that neither one of the studied alleles is susceptible to GD in the Lebanese patients. As suggested by Chen et al (2000), the discordance of the results among different studies may be due to the complex interaction of HLA molecules with environmental factors, to initiate the pathogenic process of the disease.…”

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].…”