CTLA-4 (CD152) gene polymorphism at position 49 in exon 1 in Graves' disease in a Polish population of the Lower Silesian region.
BACKGROUND
Graves' disease ((GD)is an autoimmune disease believed to be caused by a combination of environmental and genetic factors. The gene encoding cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)is one of the candidate genes for conferring susceptibility to thyroid autoimmunity. he aim of the study was to investigate the association between the exon 1 CTLA-4 gene polymorphism A(49)G and susceptibility to GD and Graves ' ophthalmopathy (GO)as well as its severity in a Polish population of the Lower Silesia region.


METHODS
We analyzed the A(49)G exon 1 CTLA-4 gene polymorphism in 99 unrelated Polish patients with GD, of whom 50 had clinically evident GO (NOSPECS class III and higher), and 154 matched healthy subjects from the Lower Silesia region. Genomic DNA was isolated from whole frozen blood using the NucleoSpin Blood kit. A/G transition was genotyped by polymerase chain reaction followed by labeling with the SnaPshot kit of PE Applied Biosystems and detected using an ABI PRISM 310 capillary genetic analyzer.


RESULTS
The distribution of CTLA-4 exon 1 A(49)G enotype, allele, and phenotypic frequencies did not differ between patients with GD and healthy subjects. There was a significantly lower frequency of the AA genotype in the group of patients with clinically evident GO than in patients without severe GO (22% vs. 43%; p=0.02, OR=2.6).


CONCLUSIONS
Our results showed that the AA genotype in patients with GD is associated with a lower risk of GO severity.
Frydecka
Irena
I
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland. frydecka@hemat.am.wroc.pl
Daroszewski
Jacek
J
Suwalska
Katarzyna
K
Zołedziowska
Magdalena
M
Tutak
Anna
A
Słowik
Mirosław
M
Potoczek
Stanisław
S
Dobosz
Tadeusz
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D005091:Exons; D005260:Female; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human