GENETIC-FACTORS IN AUTOIMMUNE THYROID-DISEASE ANALYZED BY RESTRICTION-FRAGMENT-LENGTH-POLYMORPHISMS OF CANDIDATE GENES

被引:70
作者
MANGKLABRUKS, A
COX, N
DEGROOT, LJ
机构
[1] UNIV CHICAGO, DEPT MED,THYROID STUDY UNIT,BOX 138, 5841 S MARYLAND AVE, CHICAGO, IL 60637 USA
[2] UNIV CHICAGO, HOWARD HUGHES MED RES INST, CHICAGO, IL 60637 USA
关键词
D O I
10.1210/jcem-73-2-236
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Possible genetic effects on the development of autoimmune thyroid disease were studied by analysis of restriction fragment length polymorphisms (RFLPs) of candidate genes. Peripheral blood leukocyte DNA was obtained from 65 caucasian patients with Graves' disease, 63 caucasian patients with Hashimoto's thyroiditis, and 65 caucasian controls. RFLP analysis was carried out on genomic DNA, using probes for DR-beta, DQ-alpha, DQ-beta, DP-alpha, DP-beta, T-cell receptor TCR-alpha, and thyroid peroxidase. The methodology allowed HLA-DR and DQ typing and provided information on specific RFLP patterns related to T cell receptor (TCR)alpha, DP-alpha and -beta, and -beta, and thyroid peroxidase. HLA-DR3 frequency was significantly increased in patients with Graves' disease, as reported previously by others, but neither DNA-derived subtype of DR3 was differentially increased. HLA-DQw2 was also present in increased frequency because of its linkage disequilibrium with HLA-DR3. It is uncertain whether the primary susceptibility is with DQ, DR, or another nearby locus. Susceptibility was not related in these studies to genetic loci recognized in these studies involving DQ-alpha, DP, TCR, or thyroid peroxidase. A significant linkage disequilibrium between DR3 and a specific DX-alpha RFLP was observed in Graves' disease, but is believed to be representative of a generalized linkage disequilibrium between DR3 and DX-alpha, rather than a specific abnormality in Graves' disease. Previous studies indicating association with specific TCR RFLPs could not be reproduced. The relative risk for carriers of HLA-DR3 subtype A in this study was 7.37-fold. RFLP analysis offers the possibility of investigating linkage in a variety of candidate genes as well as established genetic relationships for potentially important subtypes. While the significant relationship with HLA-DR3/DQw2 was reconfirmed, the involvement of other genes or haplotypes could not be established.
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页码:236 / 244
页数:9
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