Analysis of Immune Regulatory Genes in Familial and Sporadic Graves’ Disease
Yoshiyuki Ban,
Erlinda S. Concepcion,
Ronald Villanueva,
David A. Greenberg,
Terry F. Davies and
Yaron Tomer
Division of Endocrinology, Diabetes, and Bone Diseases, Mount Sinai School of Medicine (Y.B., E.S.C., R.V., T.F.D., Y.T.), New York, New York 10029; and Division of Statistical Genetics, Columbia University (D.A.G.), New York, New York 10032
Address all correspondence and requests for reprints to: Dr. Yaron Tomer, Division of Endocrinology, Diabetes, and Bone Diseases, Box 1055, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, New York 10029. E-mail: yaron.tomer{at}mssm.edu.
Graves’ disease (GD) is seen in apparently sporadic andfamilial forms. At least two immune regulatory genes are associatedwith GD, human leukocyte antigen (HLA) and cytotoxic T lymphocyteantigen-4 (CTLA-4). The aim of our study was to examine thecontributions of HLA and CTLA-4 to the familial clustering ofGD by analyzing them for association with familial and sporadicGD. We analyzed 160 Caucasian GD patients (69 familial and 91sporadic), and 150 matched controls. Analysis of all GD patientsdemonstrated significant associations between GD and HLA-DR3[P = 9.0 x 10–7; relative risk (RR) = 3.8] and two CTLA-4single nucleotide polymorphisms (SNPs), A/G49 SNP (P = 0.03;RR = 1.5), and CT60 SNP (P = 0.03; RR = 1.4). Moreover, therewas evidence for joint susceptibility to risk between HLA-DR3and CTLA-4, giving a combined RR of 5.9. Subset analysis demonstratedno significant difference between the frequencies of HLA-DR3and the susceptibility alleles of CTLA-4 A/G49 and CT60 SNPsin the familial and sporadic GD subsets (P > 0.05). Theseresults suggested that HLA-DR3 and CTLA-4 conferred a generalincreased risk for GD in both the sporadic and familial forms,and that the risk conferred by them was additive. However, HLA-DR3and CTLA-4 did not have a stronger effect in the familial GDpatients, suggesting that additional genes must contribute tothe aggregation of GD within families.
This article has been cited by other articles:
J. Daroszewski, E. Pawlak, L. Karabon, I. Frydecka, A. Jonkisz, M. Slowik, and M. Bolanowski 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.,
November 1, 2009;
161(5):
787 - 793.
[Abstract][Full Text][PDF]
F. K. Kavvoura, T. Akamizu, T. Awata, Y. Ban, D. A. Chistiakov, I. Frydecka, A. Ghaderi, S. C. Gough, Y. Hiromatsu, R. Ploski, et al. Cytotoxic T-Lymphocyte Associated Antigen 4 Gene Polymorphisms and Autoimmune Thyroid Disease: A Meta-Analysis
J. Clin. Endocrinol. Metab.,
August 1, 2007;
92(8):
3162 - 3170.
[Abstract][Full Text][PDF]
P. Vigano, D. Lattuada, E. Somigliana, A. Abbiati, M. Candiani, and A. M. Di Blasio Variants of the CTLA4 gene that segregate with autoimmune diseases are not associated with endometriosis
Mol. Hum. Reprod.,
October 1, 2005;
11(10):
745 - 749.
[Abstract][Full Text][PDF]
J. I. Shin, J. M. Park, J. S. Lee, D. H. Kim, and H. J. Jeong Development of Graves' disease during cyclosporin treatment for severe Henoch-Schonlein nephritis
Nephrol. Dial. Transplant.,
September 1, 2005;
20(9):
2014 - 2015.
[Full Text][PDF]
B. Golden, L. Levin, Y. Ban, E. Concepcion, D. A. Greenberg, and Y. Tomer Genetic Analysis of Families with Autoimmune Diabetes and Thyroiditis: Evidence for Common and Unique Genes
J. Clin. Endocrinol. Metab.,
August 1, 2005;
90(8):
4904 - 4911.
[Abstract][Full Text][PDF]
Y.-C. Weng, M.-J. Wu, and W.-S. Lin CT60 Single Nucleotide Polymorphism of the CTLA-4 Gene Is Associated with Susceptibility to Graves' Disease in the Taiwanese Population
Ann. Clin. Lab. Sci.,
January 1, 2005;
35(3):
259 - 264.
[Abstract][Full Text][PDF]
