HLA-DRB1*08, DRB1*03/DRB3 0101, and DRB3*0202 are Susceptibility genes for graves' disease in north American Caucasians, whereas DRB1*07 is protective

Q. Y. Chen, W. Huang, Jin-Xiong She, F. Baxter, R. Volpe, N. K. Maclaren

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Abstract

Graves' disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves' disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 ± 4.8 yr; n = 30) and later age at onset of disease (38.8 ± 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB1*03 was associated with Graves' disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB1*08 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves' (P = 0.001; X2 = 10.8). DRB3 was highly associated with Graves' in both groups of patients (P = 0.009; X2 = 6.83 and P = 0.0015; X2 = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB3*0101 and DRB3*0202 were increased over the entire cohort, that of DRB3*0301 was not. Significant P values were found for DRB3*0101 in patients with early-onset and for DRB3*0202 in patients with later onset of Graves' disease. When the haplotypes of DRB1*03-DRB3 of all subtypes were removed for analysis (all DRB1*03 positive also had DRB3*0101), the frequency of DRB3*0202 remained significantly higher in the patients with later onset of Graves' disease than in controls (P = 0.0043; X2 = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB1*07 was negatively associated with both groups of patients (P = 0.024; X2 = 5.10 and P = 0.0085; X2 = 6.93). These data suggest that DRB3*0202 is more likely to be the primary susceptible locus than DRB1*03 for patients with later onset of Graves' disease.

Original languageEnglish (US)
Pages (from-to)3182-3186
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume84
Issue number9
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

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HLA-DRB1 Chains
Graves Disease
Genes
HLA-D Antigens
Age of Onset
Haplotypes
Canada
Odds Ratio
Genotype

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

HLA-DRB1*08, DRB1*03/DRB3 0101, and DRB3*0202 are Susceptibility genes for graves' disease in north American Caucasians, whereas DRB1*07 is protective. / Chen, Q. Y.; Huang, W.; She, Jin-Xiong; Baxter, F.; Volpe, R.; Maclaren, N. K.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 84, No. 9, 01.01.1999, p. 3182-3186.

Research output: Contribution to journalArticle

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abstract = "Graves' disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves' disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 ± 4.8 yr; n = 30) and later age at onset of disease (38.8 ± 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB1*03 was associated with Graves' disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB1*08 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves' (P = 0.001; X2 = 10.8). DRB3 was highly associated with Graves' in both groups of patients (P = 0.009; X2 = 6.83 and P = 0.0015; X2 = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB3*0101 and DRB3*0202 were increased over the entire cohort, that of DRB3*0301 was not. Significant P values were found for DRB3*0101 in patients with early-onset and for DRB3*0202 in patients with later onset of Graves' disease. When the haplotypes of DRB1*03-DRB3 of all subtypes were removed for analysis (all DRB1*03 positive also had DRB3*0101), the frequency of DRB3*0202 remained significantly higher in the patients with later onset of Graves' disease than in controls (P = 0.0043; X2 = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB1*07 was negatively associated with both groups of patients (P = 0.024; X2 = 5.10 and P = 0.0085; X2 = 6.93). These data suggest that DRB3*0202 is more likely to be the primary susceptible locus than DRB1*03 for patients with later onset of Graves' disease.",
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AU - Huang, W.

AU - She, Jin-Xiong

AU - Baxter, F.

AU - Volpe, R.

AU - Maclaren, N. K.

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N2 - Graves' disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves' disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 ± 4.8 yr; n = 30) and later age at onset of disease (38.8 ± 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB1*03 was associated with Graves' disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB1*08 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves' (P = 0.001; X2 = 10.8). DRB3 was highly associated with Graves' in both groups of patients (P = 0.009; X2 = 6.83 and P = 0.0015; X2 = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB3*0101 and DRB3*0202 were increased over the entire cohort, that of DRB3*0301 was not. Significant P values were found for DRB3*0101 in patients with early-onset and for DRB3*0202 in patients with later onset of Graves' disease. When the haplotypes of DRB1*03-DRB3 of all subtypes were removed for analysis (all DRB1*03 positive also had DRB3*0101), the frequency of DRB3*0202 remained significantly higher in the patients with later onset of Graves' disease than in controls (P = 0.0043; X2 = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB1*07 was negatively associated with both groups of patients (P = 0.024; X2 = 5.10 and P = 0.0085; X2 = 6.93). These data suggest that DRB3*0202 is more likely to be the primary susceptible locus than DRB1*03 for patients with later onset of Graves' disease.

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