| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
Department of Medicine, University of Birmingham at Birmingham Heartlands (A.H.B., S.C.L.G., P.M.D.) and Queen Elizabeth Hospitals (J.M.H., A.A., J.C.-S., J.D., A.D., M.C.S., A.H.B., J.A.F., S.C.L.G.); the Department of Statistics, University of Birmingham (R.L.H.), Birmingham, United Kingdom B9 5SS; Royal Bournemouth Hospital (M.A.), Bournemouth, United Kingdom; and Royal Devon and Exeter Hospitals (A.H., K.M.), Exeter, United Kingdom
Address all correspondence and requests for reprints to: Dr. S. C. L. Gough, Department of Medicine, University of Birmingham, Birmingham Heartlands Hospital, Bordesley Green East, Birmingham, United Kingdom B9 5SS. E-mail: s.c.gough{at}bham.ac.uk
Case-control studies suggest that the CTLA-4 gene may be
a susceptibility locus for Graves’ disease. The previously reported
A/G polymorphism at position 49 in exon 1 of the CTLA-4
gene was, therefore, investigated in a case-control (n = 743) and
family-based (n = 179) dataset of white Caucasian subjects with
Graves’ disease. The relationship between CTLA-4
genotype and severity of thyroid dysfunction at diagnosis was also
investigated. An increase in frequency of the G (alanine) allele was
seen in Graves’ patients compared with control subjects (42%
vs. 31.5%, respectively; corrected
P < 0.0002; odds ratio = 1.58), and a
significant difference in the distribution of GG, GA, and AA genotypes
was observed between the groups (
2 = 21.7;
corrected P < 0.00003). Increased transmission of
the G allele was seen from heterozygous parents to affected offspring
compared to unaffected offspring (2 = 5.7;
P = 0.025). Circulating free T4
concentrations at diagnosis were significantly associated with
CTLA-4 genotype (F = 3.26; P =
0.04). These results support the hypothesis that CTLA-4 may play a role
in regulating self-tolerance by the immune system and in the
pathogenesis of autoimmune disorders such as Graves’ disease.
This article has been cited by other articles:
 |
|
 |
|
  A. Huber, F. Menconi, S. Corathers, E. M. Jacobson, and Y. Tomer Joint Genetic Susceptibility to Type 1 Diabetes and Autoimmune Thyroiditis: from Epidemiology to Mechanisms Endocr. Rev., October 1, 2008; 29(6): 697 - 725. [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.-W. Wang, I-Y. Chen, R.-T. Liu, C.-J. Hsieh, E. Hsi, and S.-H. H. Juo Cytotoxic T Lymphocyte-Associated Molecule-4 Gene Polymorphism and Hyperthyroid Graves' Disease Relapse after Antithyroid Drug Withdrawal: A Follow-Up Study J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2513 - 2518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.S. C. Graham, A.K. Wong, N.J. McHugh, J.C. Whittaker, and T. J. Vyse Evidence for unique association signals in SLE at the CD28-CTLA4-ICOS locus in a family-based study Hum. Mol. Genet., November 1, 2006; 15(21): 3195 - 3205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Taylor, S. C. Gough, P. J. Hunt, T. H. Brix, K. Chatterjee, J. M. Connell, J. A. Franklyn, L. Hegedus, B. G. Robinson, W. M. Wiersinga, et al. A Genome-Wide Screen in 1119 Relative Pairs with Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 646 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Atan, S. J. Turner, D. J. Kilmartin, J. V. Forrester, J. Bidwell, A. D. Dick, and A. J. Churchill Cytokine Gene Polymorphism in Sympathetic Ophthalmia Invest. Ophthalmol. Vis. Sci., November 1, 2005; 46(11): 4245 - 4250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C E Jennings, C J Owen, V Wilson, and S H S Pearce A haplotype of the CYP27B1 promoter is associated with autoimmune Addison's disease but not with Graves' disease in a UK population J. Mol. Endocrinol., June 1, 2005; 34(3): 859 - 863. [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]
|
|
|
|
|
|
S. M. Anjos, M.-C. Tessier, and C. Polychronakos Association of the Cytotoxic T Lymphocyte-Associated Antigen 4 Gene with Type 1 Diabetes: Evidence for Independent Effects of Two Polymorphisms on the Same Haplotype Block J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6257 - 6265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ban, E. S. Concepcion, R. Villanueva, D. A. Greenberg, T. F. Davies, and Y. Tomer Analysis of Immune Regulatory Genes in Familial and Sporadic Graves' Disease J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4562 - 4568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.-W. Wang, R.-T. Liu, S.-H. H. Juo, S.-T. Wang, Y.-H. Hu, C.-J. Hsieh, M.-H. Chen, I-Y. Chen, and C.-L. Wu Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves' Hyperthyroidism after Antithyroid Withdrawal J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 169 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Prabhakar, R. S. Bahn, and T. J. Smith Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy Endocr. Rev., December 1, 2003; 24(6): 802 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tomer and T. F. Davies Searching for the Autoimmune Thyroid Disease Susceptibility Genes: From Gene Mapping to Gene Function Endocr. Rev., October 1, 2003; 24(5): 694 - 717. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kretowski, N. Wawrusiewicz, K. Mironczuk, J. Mysliwiec, M. Kretowska, and I. Kinalska Intercellular Adhesion Molecule 1 Gene Polymorphisms in Graves' Disease J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4945 - 4949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Collins, J. M. Heward, J. Carr-Smith, J. Daykin, J. A. Franklyn, and S. C. L. Gough Association of a Rare Thyroglobulin Gene Microsatellite Variant with Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5039 - 5042. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Jin, W. Teng, S. Ben, X. Xiong, J. Zhang, S. Xu, Y. Y. Shugart, L. Jin, J. Chen, and W. Huang Genome-Wide Scan of Graves' Disease: Evidence for Linkage on Chromosome 5q31 in Chinese Han Pedigrees J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1798 - 1803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Vaidya, P. Kendall-Taylor, and S. H. S. Pearce The Genetics of Autoimmune Thyroid Disease J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5385 - 5397. [Full Text] [PDF]
|
|
|
|
 |
|
 S. Anjos, A. Nguyen, H. Ounissi-Benkalha, M.-C. Tessier, and C. Polychronakos A Common Autoimmunity Predisposing Signal Peptide Variant of the Cytotoxic T-lymphocyte Antigen 4 Results in Inefficient Glycosylation of the Susceptibility Allele J. Biol. Chem., November 22, 2002; 277(48): 46478 - 46486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Collin, K. Kaukinen, M. Valimaki, and J. Salmi Endocrinological Disorders and Celiac Disease Endocr. Rev., August 1, 2002; 23(4): 464 - 483. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Kinjo, N. Takasu, I. Komiya, T. Tomoyose, M. Takara, T. Kouki, Y. Shimajiri, K. Yabiku, and H. Yoshimura Remission of Graves' Hyperthyroidism and A/G Polymorphism at Position 49 in Exon 1 of Cytotoxic T Lymphocyte-Associated Molecule-4 Gene J. Clin. Endocrinol. Metab., June 1, 2002; 87(6): 2593 - 2596. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Vaidya, S. H. S. Pearce, S. Charlton, N. Marshall, A. D. Rowan, I. D. Griffiths, P. Kendall-Taylor, T. E. Cawston, and S. Young-Min An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies Rheumatology, February 1, 2002; 41(2): 180 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Kacem, N. Kaddour, F.-Z. Adyel, Z. Bahloul, and H. Ayadi HLA-DQB1 CAR1/CAR2, TNFa IR2/IR4 and CTLA-4 polymorphisms in Tunisian patients with rheumatoid arthritis and Sjogren's syndrome Rheumatology, December 1, 2001; 40(12): 1370 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. F. Muller, H. A. Drexhage, and A. Berghout Postpartum Thyroiditis and Autoimmune Thyroiditis in Women of Childbearing Age: Recent Insights and Consequences for Antenatal and Postnatal Care Endocr. Rev., October 1, 2001; 22(5): 605 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Holopainen and J. A. Partanen Technical Note: Linkage Disequilibrium and Disease-Associated CTLA4 Gene Polymorphisms J. Immunol., September 1, 2001; 167(5): 2457 - 2458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sakai, S. Shirasawa, N. Ishikawa, K. Ito, H. Tamai, K. Kuma, T. Akamizu, M. Tanimura, K. Furugaki, K. Yamamoto, et al. Identification of susceptibility loci for autoimmune thyroid disease to 5q31-q33 and Hashimoto's thyroiditis to 8q23-q24 by multipoint affected sib-pair linkage analysis in Japanese Hum. Mol. Genet., June 1, 2001; 10(13): 1379 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Tomer, D. A. Greenberg, G. Barbesino, E. Concepcion, and T. F. Davies CTLA-4 and Not CD28 Is a Susceptibility Gene for Thyroid Autoantibody Production J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1687 - 1693. [Abstract] [Full Text]
|
|
|
|
|
|
M. K. Oaks and K. M. Hallett Cutting Edge: A Soluble Form of CTLA-4 in Patients with Autoimmune Thyroid Disease J. Immunol., May 15, 2000; 164(10): 5015 - 5018. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Nithiyananthan, J. M. Heward, A. Allahabadia, A. H. Barnett, J. A. Franklyn, and S. C. L. Gough A Heterozygous Deletion of the Autoimmune Regulator (AIRE1) Gene, Autoimmune Thyroid Disease, and Type 1 Diabetes: No Evidence for Association J. Clin. Endocrinol. Metab., March 1, 2000; 85(3): 1320 - 1322. [Abstract] [Full Text]
|
|
|
|
|
|
Mapping the Major Susceptibility Loci for Familial Graves' and Hashimoto's Diseases: Evidence for Genetic Heterogeneity and Gene Interactions J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4656 - 4664. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
