PMID- 14751028
OWN - NLM
STAT- MEDLINE
DCOM- 20040804
LR  - 20131121
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 13
IP  - 12
DP  - 2003 Dec
TI  - CTLA-4 AT-repeat polymorphism reduces the inhibitory function of CTLA-4 in 
      Graves' disease.
PG  - 1083-9
AB  - Graves' disease (GD) is thought to be an autoimmune disease with a strong genetic 
      component. Candidate genes include human leukocyte antigen (HLA) class II genes 
      and CTLA-4. The CTLA-4 gene has a variable length AT-repeat polymorphism in the 
      3'-untranslated region. We previously found that the AT-repeat of 104 bp or 
      longer was associated with GD. In this study, we categorized patients with GD and 
      normal controls (NC) by genotyping the CTLA-4 AT-repeat and investigated the 
      function of CTLA-4. Peripheral blood mononuclear cells (PBMC) and DNA were 
      prepared from adult Caucasians (NC = 34, GD = 37). Genotypes of the AT-repeat 
      polymorphism were divided into three groups according to their alleles. We 
      related the CTLA-4 polymorphism in each genotype to augmentation of T-cell 
      proliferation induced by a soluble anti-CTLA-4 antibody during incubation with 
      irradiated Epstein-Barr virus (EBV)-transformed B cells. Proliferation of T cells 
      from subjects with the 86/86 bp (shorter) allele was less than T cells from 
      patients with longer alleles. The length of the AT-repeat allele correlated 
      inversely with augmentation of proliferation after CTLA-4 blockade in subjects 
      with GD. The CTLA-4 AT-repeat polymorphism affects the inhibitory function of 
      CTLA-4. The long AT-repeat allele is associated with reduced control of T-cell 
      proliferation and thus contributes to the pathogenesis of GD.
FAU - Takara, Masaki
AU  - Takara M
AD  - Thyroid Study Unit/MC3090, Department of Medicine, The University of Chicago, 
      Chicago, Illinois 60637, USA.
FAU - Kouki, Tsuyoshi
AU  - Kouki T
FAU - DeGroot, Leslie J
AU  - DeGroot LJ
LA  - eng
GR  - 2-R01-DK27384-18A1/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 5Z93L87A1R (Guanine)
RN  - JAC85A2161 (Adenine)
RN  - QR26YLT7LT (Thymine)
SB  - IM
MH  - Adenine
MH  - Adult
MH  - Antibodies, Monoclonal/pharmacology
MH  - Antigens, CD
MH  - Antigens, Differentiation/*genetics/immunology/*metabolism
MH  - B-Lymphocytes
MH  - CTLA-4 Antigen
MH  - Case-Control Studies
MH  - Cell Division
MH  - Cell Transformation, Viral
MH  - Graves Disease/*genetics/*metabolism/pathology
MH  - Guanine
MH  - Herpesvirus 4, Human
MH  - Humans
MH  - Monocytes/pathology
MH  - *Polymorphism, Genetic
MH  - Repetitive Sequences, Nucleic Acid
MH  - T-Lymphocytes/pathology
MH  - Thymine
EDAT- 2004/01/31 05:00
MHDA- 2004/08/05 05:00
CRDT- 2004/01/31 05:00
PHST- 2004/01/31 05:00 [pubmed]
PHST- 2004/08/05 05:00 [medline]
PHST- 2004/01/31 05:00 [entrez]
AID - 10.1089/10507250360731479 [doi]
PST - ppublish
SO  - Thyroid. 2003 Dec;13(12):1083-9. doi: 10.1089/10507250360731479.