Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms.

Eur J Endocrinol 2009 Nov 4;161(5):787-93. Epub 2009 Sep 4.

Department of Endocrinology, Diabetology, and Isotope Therapy, Medical University, ul. Pasteura 4, 50-367 Wroclaw, Poland.

Objective: Graves' disease (GD) is an autoimmune disorder with genetic and environmental background. CTLA-4 is a candidate gene for thyroid autoimmunity. Increased serum levels of soluble CTLA-4 (sCTLA-4) were found in some autoimmune diseases.

Aim: The aim of the study was to evaluate the relation between sCTLA-4 level and clinical manifestation of Graves' ophthalmopathy (GO), thyroid status, and CTLA-4 gene polymorphisms.

Design: Serum sCTLA-4 concentrations were determined in 93 GO patients and 93 healthy controls. In the GO group, CTLA-4 gene was genotyped in five polymorphic sites: g.319C>T, c.49A>G, CT60 by means of PRC-RFLP, Jo31, and g.*642AT(8_33) by means of minisequencing assay.

Results: Serum sCTLA-4 level was significantly higher in the GO group than in controls (median: 7.94 vs 0.00 ng/ml, P=0.000001). This level was higher in severe than in nonsevere GO (median: 10.3 vs 5.6 ng/ml, P=0.01). sCTLA-4 concentration was related neither to the activity of GO nor to thyroid function. Elevated sCTLA-4 levels were observed in carriers Jo31[G] allele (genotype GG+GT) as compared with subjects with an absence of the [G] allele (TT genotype; median: 9.18 vs 4.0 ng/ml, P=0.02). Also patients possessing CT60[G] allele (genotype GG+GA) had higher serum sCTLA-4 levels than subjects who lack the [G] allele (AA genotype; median: 8.73 vs 2.28 ng/ml, P=0.03).

Conclusions: It was shown for the first time that increased serum concentration of sCTLA-4 correlate with the severity of GO. Genetic variation in the CTLA-4 gene region in GD patients at least partially determines the level of sCTLA-4.

Download full-text PDF

Source
http://dx.doi.org/10.1530/EJE-09-0600DOI Listing
November 2009
1 Read

Publication Analysis

Top Keywords

allele genotype
16
ctla-4 gene
12
serum sctla-4
12
sctla-4
9
[g] allele
8
soluble ctla-4
8
level higher
8
genotype median
8
sctla-4 levels
8
graves' disease
8
sctla-4 level
8
increased serum
8
ctla-4
6
gene
5
serum
5
p=0000001 level
4
severe nonsevere
4
median 103
4
nonsevere median
4
103 ng/ml
4

Altmetric Statistics

Similar Publications