Cytotoxic T lymphocyte-associated molecule-4 polymorphism and relapse of Graves' hyperthyroidism after antithyroid withdrawal.
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.
Wang
Pei-Wen
PW
Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung 83305, Taiwan.
Liu
Rue-Tsuan
RT
Juo
Suh-Hang Hank
SH
Wang
Shan-Tair
ST
Hu
Ya-Hui
YH
Hsieh
Ching-Jung
CJ
Chen
Ming-Hong
MH
Chen
I-Ya
IY
Wu
Chia-Ling
CL
D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D013956:Antithyroid Agents / Q000008:administration & dosage*; D060908:CTLA-4 Antigen; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006111:Graves Disease / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008713:Methimazole / Q000008:administration & dosage; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011441:Propylthiouracil / Q000008:administration & dosage; D012008:Recurrence; D013624:Taiwan; D016896:Treatment Outcome
D015703:Antigens, CD; D000943:Antigens, Differentiation; D013956:Antithyroid Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D008713:Methimazole; D011441:Propylthiouracil