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Association of CD40 and thyroglobulin genes with later-onset Graves' disease in Taiwanese patients

¹ Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan, ROC² Department of Emergency Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Chiayi 613, Taiwan, ROC³ Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan, ROC⁴ Department of Respiratory Care, Chang Gung Institute of Technology, Chiayi 613, Taiwan, ROC⁵ Graduate Institute of Occupational Safety and Health, College of Health Sciences, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC⁶ Division of Neurology Medicine, Department of Internal Medicine, Chi-Mei Medical Center, Tainan 710, Taiwan, ROC

(Correspondence should be addressed to D-S Ke who is now at Department of Endocrinology and Metabolism, Chung-Ho Memorial Hospital, Kaohsiung Medical University, 100 Shin-Chuan 1st Road, Kaohsiung 807, Taiwan, ROC; Email: dershin{at}mail.cmu.edu.tw)

Objective: Graves' disease (GD) is known to be associated with thyroglobulin (TG) and CD40 genes. Therefore, we decided to investigate the relationship of age at onset of GD with CD40 and TG gene susceptibilities in a Taiwanese population.

Design and method: We analyzed the association of TG and CD40 polymorphisms with age at onset of GD in Taiwanese patients. We stratified patients into those with early onset (<40 years; 30.3±4.8 years; n=135) and later onset (40 years; 52.3±6.3 years; n=80) and compared the results with those of 141 normal controls.

Results: We found a significant statistical difference in the T/T genotype frequency of E33 single nucleotide polymorphism (SNP) and G/G genotype frequency of E12 SNP when compared with the control group (P<0.001). In addition, the frequencies of the T allele and TT genotype of the CD40 SNP were found to be significantly increased in GD patients who developed GD aged over 40 years than those below 40 years (allele: ²=5.299, P=0.021, OR=1.597; genotype: ²=6.168, P=0.046). By contrast, the frequencies of genotypes in the TG gene E10, E12, and E33 SNPs were not found to be significantly different in GD patients who developed GD when aged over 40 years when compared with those aged below 40 years.

Conclusions: These data suggest that the T/T genotype and T allele in the CD40 gene are more likely to be associated with late-onset GD in Taiwanese patients.