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HLA CLASS II DNA GENOTYPES IN GRAVES' DISEASE: CLUES TO INHERITANCE OF THE HLA‐LINKED COMPONENT OF SUSCEPTIBILITY
Author(s) -
FLETCHER J.,
FRANKLYN J. A.,
McLACHLAN S. M.,
YOUNG E.,
SHEPPARD M. C.
Publication year - 1988
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/j.1365-2265.1988.tb03703.x
Subject(s) - taqi , restriction fragment length polymorphism , hla dq , restriction enzyme , restriction fragment , genotype , genetics , haplotype , biology , human leukocyte antigen , immunology , microbiology and biotechnology , medicine , dna , antigen , gene
SUMMARY Restriction fragment length polymorphism analysis using DQα, DQ β and DR β cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 70 + 4.0kb DR β /Taq1 fragments (66% vs 32%; P < 0.01;corrected P < 0.06),7.0+4.0 kbDQ β /BamHI fragments (55% vs 15%; P < 0.001; corrected P <0006), and a DQα/TaqI 4.6kb fragment (75% vs 36%; P < 0.005; corrected P < 0.02). These associations could be accounted for by the known association of the B8‐DR3 haplotype with the disorder. No non‐DR3‐related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI. The 10+7‐0 + 4‐0kb DR β /TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3‐associated component of disease susceptibility (P=001). The implications of these findings are discussed with reference to models for the inheritance of the HLA‐linked component of Graves' disease susceptibility.