PMID- 8855789
OWN - NLM
STAT- MEDLINE
DCOM- 19961119
LR  - 20101118
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 81
IP  - 10
DP  - 1996 Oct
TI  - Analysis of the thyrotropin receptor as a candidate gene in familial Graves' 
      disease.
PG  - 3483-6
AB  - Familial clustering of Graves' disease indicates a genetic etiology. Searches for 
      genetic factors additional to the known human leukocyte antigen (HLA) association 
      have implicated the gene for the TSH receptor (TSHR). We analyzed the linkage and 
      association among three recently described microsatellite markers within the TSHR 
      introns in Graves' disease in large multiply affected Welsh and English families 
      (223 members, 44 affected individuals). Linkage analysis under a dominant model 
      strongly rejected the hypothesis that TSHR is linked to Graves' disease in these 
      families (lod score = -4.53). More detailed analyses also failed to provide 
      evidence for linkage; these included combined segregation and linkage analysis, 
      correction for HLA-DR3 status, allowance for the levels of thyroid autoantibodies 
      in unaffected pedigree members, consideration of a recessive model for the 
      disease, and linkage disequilibrium between disease and marker alleles. We also 
      considered the possibility of a genetic heterogeneity of Graves' disease and thus 
      analyzed separately the different families with a similar result. Although these 
      results cannot eliminate a minor role of the TSHR gene locus in the genetics of 
      Graves' disease, they argue against it being a major genetic determinant in this 
      pathology.
FAU - de Roux, N
AU  - de Roux N
AD  - Unite de Recherches Hormones et Reproduction, INSERM, U-135, Hopital de Bicetre, 
      Le Kremlin-Bicetre, France.
FAU - Shields, D C
AU  - Shields DC
FAU - Misrahi, M
AU  - Misrahi M
FAU - Ratanachaiyavong, S
AU  - Ratanachaiyavong S
FAU - McGregor, A M
AU  - McGregor AM
FAU - Milgrom, E
AU  - Milgrom E
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (Receptors, Thyrotropin)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Female
MH  - Genetic Linkage
MH  - Graves Disease/*genetics
MH  - HLA-DR3 Antigen/genetics
MH  - Humans
MH  - Lod Score
MH  - Male
MH  - Middle Aged
MH  - Receptors, Thyrotropin/*genetics
EDAT- 1996/10/01 00:00
MHDA- 1996/10/01 00:01
CRDT- 1996/10/01 00:00
PHST- 1996/10/01 00:00 [pubmed]
PHST- 1996/10/01 00:01 [medline]
PHST- 1996/10/01 00:00 [entrez]
AID - 10.1210/jcem.81.10.8855789 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1996 Oct;81(10):3483-6. doi: 10.1210/jcem.81.10.8855789.