Cytotoxic T lymphocyte-associated molecule-4 gene polymorphism and hyperthyroid Graves' disease relapse after antithyroid drug withdrawal: a follow-up study.
BACKGROUND
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.


METHODS
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.
Wang
Pei-Wen
PW
Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Chen
I-Ya
IY
Liu
Rue-Tsuan
RT
Hsieh
Ching-Jung
CJ
Hsi
Edward
E
Juo
Suh-Hang Hank
SH
D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D000943:Antigens, Differentiation / Q000235:genetics*; D013956:Antithyroid Agents / Q000627:therapeutic use*; D060908:CTLA-4 Antigen; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D006111:Graves Disease / Q000188:drug therapy* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D012008:Recurrence
D015703:Antigens, CD; D000943:Antigens, Differentiation; D013956:Antithyroid Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers