Lack of a genetic association between the CTLA-4 gene and Graves' disease in Koreans.
Graves' disease (GD) is a complex autoimmune thyroid disease with a strong genetic component. The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene, which encodes a negative regulator of the T-lymphocyte immune response, has been reported to be associated and/or linked to GD. Therefore, in order to determine the contribution of CTLA-4 in GD in Koreans, we genotyped the five single nucleotide Polymorphisms (SNPs) of the CTLA-4 gene, including +49, CT60, JO31, JO30, and JO27-1 in Korean spatients with GD and healthy controls. Two hundred seventy-eight Korean patients with GD from the Thyroid Clinic and 472 healthy controls from the Health Screening Center of Samsung Medical Center were enrolled in this study. The +49A/G polymorphism of the CTLA-4 gene exon 1 was sequenced directly and the genotyping of the remaining 4 SNPs was accomplished using a Snapshot. In addition, the association of haplotypes with a combination of the above markers was also examined in 278 Korean patients with GD and 472 controls. The results showed that there was no significant positive association between any individual SNP or haplotype comprising of the four 3 untranslated region (UTR) SNPs (CT60, JO31, JO30, and JO27-1) and GD. These data provide little support for CTLA-4 to play a role in the genetic predisposition to GD in Koreans. However, it will be necessary to validate or replicate this association in other independent large-size ethnic groups.
Cho
Hyun-Jung
HJ
Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chung
Jae Hoon
JH
Kim
In Sook
IS
Kim
Hee-Jin
HJ
Cho
Seung Hee
SH
Ki
Chang-Seok
CS
Kim
Jong-Won
JW
D020413:3' Untranslated Regions / Q000235:genetics; D000328:Adult; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People; D060908:CTLA-4 Antigen; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D007723:Korea; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
D020413:3' Untranslated Regions; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human