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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; 161(5):787-93EJ

Abstract

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.

Authors+Show Affiliations

Department of Endocrinology, Diabetology, and Isotope Therapy, Medical University, ul. Pasteura 4, 50-367 Wroclaw, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19734241

Citation

Daroszewski, Jacek, et al. "Soluble CTLA-4 Receptor an Immunological Marker of Graves' Disease and Severity of Ophthalmopathy Is Associated With CTLA-4 Jo31 and CT60 Gene Polymorphisms." European Journal of Endocrinology, vol. 161, no. 5, 2009, pp. 787-93.
Daroszewski J, Pawlak E, Karabon L, et al. 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;161(5):787-93.
Daroszewski, J., Pawlak, E., Karabon, L., Frydecka, I., Jonkisz, A., Slowik, M., & Bolanowski, M. (2009). Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms. European Journal of Endocrinology, 161(5), pp. 787-93. doi:10.1530/EJE-09-0600.
Daroszewski J, et al. 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;161(5):787-93. PubMed PMID: 19734241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Soluble CTLA-4 receptor an immunological marker of Graves' disease and severity of ophthalmopathy is associated with CTLA-4 Jo31 and CT60 gene polymorphisms. AU - Daroszewski,Jacek, AU - Pawlak,Edyta, AU - Karabon,Lidia, AU - Frydecka,Irena, AU - Jonkisz,Anna, AU - Slowik,Miroslaw, AU - Bolanowski,Marek, Y1 - 2009/09/04/ PY - 2009/9/8/entrez PY - 2009/9/8/pubmed PY - 2009/11/17/medline SP - 787 EP - 93 JF - European journal of endocrinology JO - Eur. J. Endocrinol. VL - 161 IS - 5 N2 - 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. SN - 1479-683X UR - https://www.unboundmedicine.com/medline/citation/19734241/Soluble_CTLA_4_receptor_an_immunological_marker_of_Graves'_disease_and_severity_of_ophthalmopathy_is_associated_with_CTLA_4_Jo31_and_CT60_gene_polymorphisms_ L2 - https://eje.bioscientifica.com/doi/10.1530/EJE-09-0600 DB - PRIME DP - Unbound Medicine ER -