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Cytotoxic T Lymphocyte-Associated Molecule-4 Gene Polymorphism and Hyperthyroid Graves’ Disease Relapse after Antithyroid Drug Withdrawal: A Follow-Up Study

Division of Endocrinology and Metabolism (P.-W.W., I.-Y.C., R.-T.L., C.-J.H.), Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan; and Department of Medical Research (E.H., S.-H.H.J.), Kaohsiung Medical University Hospital, and Graduate Institute of Medical Genetics (E.H., S.-H.H.J.), Kaohsiung Medical University, Kaohsiung 807, Taiwan

Address all correspondence and requests for reprints to: Dr. Suh-Hang H. Juo, Kaohsiung Medical University, 100 TzYou First Road, Kaohsiung City 807, Taiwan. E-mail: shj34{at}columbia.edu.

Context: We previously showed an association between the exon1 +49 A/G single nucleotide polymorphism (SNP) and the relapse of Graves’ disease (GD). The G allele was associated with early relapse.

Objective: In this follow-up study, we sought to replicate the result by genotyping nine additional polymorphisms and recruiting another 60 GD patients.

Design and Participants: The GD patients were divided into three groups: recurred within 9 months, between 10–36 months, and more than 36 months. There were 65 patients with early recurrence, 55 with medium recurrence, and 88 with late recurrence. Although several SNPs were associated with recurrence, the most significant marker was still exon1 +49 A/G. Separate analysis of the genotypes for the 60 newly enrolled patients indicated that our present study was not biased by the previous samples. Once exon1 +49 A/G was included in the model to predict recurrence, other markers would not add more predictive information. Haplotype analysis did not show an additional value once exon1 +49 A/G was compulsorily included.

Results: Multivariate logistic regression analysis showed that GG genotype of exon1 +49 A/G SNP had an adjusted odds ratio of 2.2 (95% confidence interval, 1.1–4.4) compared with the combined group of GA plus AA. Other significant predictors were large goiter size at the end of the treatment and positive TSH-binding inhibitory Ig at the end of the treatment.

Conclusions: This follow-up study confirms the usefulness of the exon1 +49 A/G SNP of the cytotoxic T lymphocyte-associated molecule-4 gene in predicting recurrence after cessation of treatment. There is no additional power by including other polymorphisms to predict recurrence.

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				F. Kaguelidou, C. Alberti, M. Castanet, M.-A. Guitteny, P. Czernichow, J. Leger, and for the French Childhood Graves' Disease Study Gro Predictors of Autoimmune Hyperthyroidism Relapse in Children after Discontinuation of Antithyroid Drug Treatment J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3817 - 3826. [Abstract] [Full Text] [PDF]