Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves' Hyperthyroidism after Antithyroid Withdrawal

Pei Wen Wang, Rue Tsuan Liu, Suh Hang Hank Juo, Shan-Tair Wang, Ya Hui Hu, Ching Jung Hsieh, Ming Hong Chen, I. Ya Chen, Chia Ling Wu

Research output: Contribution to journalArticle

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Abstract

We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39% in groups 1,2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.

Original languageEnglish
Pages (from-to)169-173
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume89
Issue number1
DOIs
Publication statusPublished - 2004 Jan 1

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T-cells
Cytotoxic T-Lymphocytes
Hyperthyroidism
Polymorphism
Graves Disease
Recurrence
Genotype
Molecules
Nucleotides
Single Nucleotide Polymorphism
Genes
Regression analysis
Logistics
Exons
Goiter
Therapeutics
Gene Frequency
Logistic Models
Alleles
Odds Ratio

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Wang, Pei Wen ; Liu, Rue Tsuan ; Juo, Suh Hang Hank ; Wang, Shan-Tair ; Hu, Ya Hui ; Hsieh, Ching Jung ; Chen, Ming Hong ; Chen, I. Ya ; Wu, Chia Ling. / Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves' Hyperthyroidism after Antithyroid Withdrawal. In: Journal of Clinical Endocrinology and Metabolism. 2004 ; Vol. 89, No. 1. pp. 169-173.
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abstract = "We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79{\%} to 64{\%} and 39{\%} in groups 1,2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0{\%}; A/G, 20.8{\%}; G/G, 45.5{\%}; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95{\%} confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.",
author = "Wang, {Pei Wen} and Liu, {Rue Tsuan} and Juo, {Suh Hang Hank} and Shan-Tair Wang and Hu, {Ya Hui} and Hsieh, {Ching Jung} and Chen, {Ming Hong} and Chen, {I. Ya} and Wu, {Chia Ling}",
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Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves' Hyperthyroidism after Antithyroid Withdrawal. / Wang, Pei Wen; Liu, Rue Tsuan; Juo, Suh Hang Hank; Wang, Shan-Tair; Hu, Ya Hui; Hsieh, Ching Jung; Chen, Ming Hong; Chen, I. Ya; Wu, Chia Ling.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 89, No. 1, 01.01.2004, p. 169-173.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cytotoxic T Lymphocyte-Associated Molecule-4 Polymorphism and Relapse of Graves' Hyperthyroidism after Antithyroid Withdrawal

AU - Wang, Pei Wen

AU - Liu, Rue Tsuan

AU - Juo, Suh Hang Hank

AU - Wang, Shan-Tair

AU - Hu, Ya Hui

AU - Hsieh, Ching Jung

AU - Chen, Ming Hong

AU - Chen, I. Ya

AU - Wu, Chia Ling

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N2 - We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39% in groups 1,2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.

AB - We studied the A/G single nucleotide polymorphism (SNP) at position 49 in exon 1 of the cytotoxic T lymphocyte-associated molecule-4 gene in 148 Chinese Graves' disease (GD) patients and 171 controls. Our primary aim was to test for the association of this SNP with the relapse of the hyperthyroidism after antithyroid withdrawal. Our secondary aim was to investigate the relationship between GD patients and controls according to the SNP genotypes. All GD patients were divided into the following three groups according to the time of relapse after drug discontinuation: group 1, early relapse within 9 months; group 2, relapse between 10 and 36 months; and group 3, relapse 3 or more years after discontinuation of treatment. There was a significant difference of genotype frequencies (P < 0.001) and allele frequencies (P < 0.001) among the three groups of patients. The frequency of the G/G genotype decreased from 79% to 64% and 39% in groups 1,2, and 3, respectively. Compared with controls, a strong association (P < 0.001) of G allele was found for group 1, and moderate significance (P = 0.04) was found for group 2, but no association (P = 0.33) was found for group 3. At the end of treatment, the percentage of patients with persistent TSH-receptor antibody was statistically different (A/A, 9.0%; A/G, 20.8%; G/G, 45.5%; P = 0.004). Using 3 yr as the cutoff point for multivariate logistic regression analysis, we found that the G/G genotype (adjusted odds ratio, 3.1 compared with A/G plus A/A; 95% confidence interval, 1.3-7.1), larger goiter size at the end of treatment, and positive TSH-receptor antibody at the end of treatment were independent risk factors of recurrence. We conclude that the A/G polymorphism of the cytotoxic T lymphocyte-associated molecule-4 gene affects the progress of GD. The G/G genotype is associated with poor outcome.

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