PMID- 15785242
OWN - NLM
STAT- MEDLINE
DCOM- 20051121
LR  - 20221207
IS  - 1050-7256 (Print)
IS  - 1050-7256 (Linking)
VI  - 15
IP  - 3
DP  - 2005 Mar
TI  - CT60 single nucleotide polymorphisms of the cytotoxic T-lymphocyte-associated 
      antigen-4 gene region is associated with Graves' disease in an Italian 
      population.
PG  - 232-8
AB  - Graves' disease (GD) is an autoimmune and polygenic disorder. Several studies 
      have shown that human leukocyte antigen (HLA) class II and the cytotoxic 
      T-lymphocyte-associated antigen-4 (CTLA-4) gene are involved in the genetic 
      susceptibility. We performed a case control study on 150 patients with GD and 301 
      controls, matched for age and gender, to verify the association of three 
      polymorphisms located in CTLA-4 region (A49G, [AT](n)-3'UTR, and CT60) and of 
      HLA-DRB1 and DQB1 loci with the disease in an Italian population. The prevalence 
      of patients with GD carrying the G allele of CT60 was significantly higher 
      compared to control subjects (p = 0.02, odds ratio [OR] = 1.82). The allelic 
      frequency of the G allele of CT60 was also significantly higher in patients with 
      GD (p = 0.02). The G allele frequency of A49G in patients was significantly 
      higher compared to control subjects (p = 0.04). The 280 allele phenotype 
      frequency of (AT)(n)-3'UTR was also significantly higher in patients (p = 0.04). 
      The G allele of A49G, the G allele of CT60, and the 280 allele of (AT)(n)-3'UTR 
      microsatellite were significantly increased in patients with GD with 
      thyroid-associated ophthalmopathy (TAO) compared to controls (p = 0.04, p = 0.03, 
      and p = 0.02, respectively), however, we did not find any significant difference 
      between TAO and non-TAO patients. We also found the HLA-DRB1*03 allele to be 
      associated with GD; interestingly, the association of the CTLA-4 markers was 
      independent from the HLA DRB1*03 status. These results highlight the role of the 
      CTLA-4 locus, in addition to HLA, in the susceptibility to GD. Inside the CTLA-4 
      region, CT60 appears to be the most associated polymorphism to GD, however, 
      further studies are needed to identify the etiologic variant.
FAU - Petrone, Antonio
AU  - Petrone A
AD  - Department of Clinical Science, University of Rome La Sapienza, 00161 Rome, 
      Italy.
FAU - Giorgi, Gabriele
AU  - Giorgi G
FAU - Galgani, Andrea
AU  - Galgani A
FAU - Alemanno, Irene
AU  - Alemanno I
FAU - Corsello, Salvatore M
AU  - Corsello SM
FAU - Signore, Alberto
AU  - Signore A
FAU - Di Mario, Umberto
AU  - Di Mario U
FAU - Nistico, Lorenza
AU  - Nistico L
FAU - Cascino, Isabella
AU  - Cascino I
FAU - Buzzetti, Raffaella
AU  - Buzzetti R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Thyroid
JT  - Thyroid : official journal of the American Thyroid Association
JID - 9104317
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation)
RN  - 0 (CTLA-4 Antigen)
RN  - 0 (CTLA4 protein, human)
RN  - 0 (DNA Primers)
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Antigens, CD
MH  - Antigens, Differentiation/*genetics
MH  - CTLA-4 Antigen
MH  - DNA Primers
MH  - Gene Frequency
MH  - Graves Disease/*genetics/*immunology
MH  - HLA-DQ Antigens/genetics
MH  - HLA-DQ beta-Chains
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Histocompatibility Testing
MH  - Humans
MH  - Italy
MH  - Microsatellite Repeats
MH  - Phenotype
MH  - Polymerase Chain Reaction
MH  - *Polymorphism, Single Nucleotide
MH  - Reference Values
MH  - White People
EDAT- 2005/03/24 09:00
MHDA- 2005/12/13 09:00
CRDT- 2005/03/24 09:00
PHST- 2005/03/24 09:00 [pubmed]
PHST- 2005/12/13 09:00 [medline]
PHST- 2005/03/24 09:00 [entrez]
AID - 10.1089/thy.2005.15.232 [doi]
PST - ppublish
SO  - Thyroid. 2005 Mar;15(3):232-8. doi: 10.1089/thy.2005.15.232.