Linkage disequilibrium between the human leukocyte antigen class II region of the major histocompatibility complex and Graves' disease: Replication using a population case control and family-based study
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Heward, JM
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Heward, JM
Allahabadia, A
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Allahabadia, A
Daykin, J
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Daykin, J
Carr-Smith, J
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Carr-Smith, J
Daly, A
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Daly, A
Armitage, M
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Armitage, M
Dodson, PM
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Dodson, PM
Sheppard, MC
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Sheppard, MC
Barnett, AH
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Barnett, AH
Franklyn, JA
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Franklyn, JA
Gough, SCL
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机构:Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
Gough, SCL
机构:
[1] Univ Birmingham, Birmingham Heartlands Hosp, Dept Med, Birmingham B9 5SS, W Midlands, England
[2] Univ Birmingham, Queen Elizabeth Hosp, Dept Med, Birmingham B15 2TH, W Midlands, England
[3] Royal Bournemouth Hosp, Bournemouth, Dorset, England
Early case control studies found association of the DRB1 allele, DR3, with Graves' disease (GD). Recent reports, claim the DQA1 allele, DQA1*0501, to be the primary susceptibility determinant within the human leukocyte antigen (HLA) class II region. We typed 228 GD patients, 364 controls, and 98 families (parents, GD, and unaffected sibling) at the DRB1, DQB1, and DQA1 loci. The case control study showed an increased frequency in GD, compared to controls, of DRB1*0304 (47% vs. 24%; pc < 1.4 x 10(-5)), DQB1*02 (58% vs. 46%; pc < 0.035), DQB1*0301/4(42% vs. 28%; pc ( 3.5 x 10(-8)) and DQA1*0501(67%, vs. 39%;pe < 7 x 10(-6)). The DRB1*0304-DQB1*02-DQA1*0501 haplotype was increased in GD (47%) vs. controls (24%; pc < 1.8 x 10(-5); odds ratio = 2.72). No independent association of these alleles was observed. Preferential transmission of DRB1*0304-DQB1*02-DQA1*0501; from parents heterozygous for the haplotype to GD siblings (72%) was seen in the families chi(2) = 11.95; 1 d.f.; P = 0.0005). Lack of preferential transmission to unaffected siblings (53%; chi(2) = 0.19; 1 d.f.;P = NS) excluded segregation distortion. These results show that linkage disequilibrium between GD and the HLA class II region is due to the extended haplotype DRB1*0304-DQB1*'02-DQA1*0501.
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Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USADana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
Schulze, Monika-Sarah E. D.
Anders, Anne-Kathrin
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Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
Harvard Univ, Sch Med, Program Immunol, Boston, MA USADana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
Anders, Anne-Kathrin
Sethi, Dhruv K.
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Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USADana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA
Sethi, Dhruv K.
Call, Melissa J.
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Univ Melbourne, Struct Biol Div, Eliza Hall Inst Med Res, Parkville, Vic 3052, AustraliaDana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA