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 language | English (US) |
|---|---|
| Pages (from-to) | 3182-3186 |
| Number of pages | 5 |
| Journal | Journal of Clinical Endocrinology and Metabolism |
| Volume | 84 |
| Issue number | 9 |
| DOIs | |
| State | Published - Jan 1 1999 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - 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
AU - Chen, Q. Y.
AU - Huang, W.
AU - She, Jin-Xiong
AU - Baxter, F.
AU - Volpe, R.
AU - Maclaren, N. K.
PY - 1999/1/1
Y1 - 1999/1/1
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0033237644&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033237644&partnerID=8YFLogxK
U2 - 10.1210/jc.84.9.3182
DO - 10.1210/jc.84.9.3182
M3 - Article
VL - 84
SP - 3182
EP - 3186
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 9
ER -