J Korean Soc Endocrinol.  1999 Mar;14(1):40-52.

Cytotoxic T Lymphocyte Antigen-4 (CTla-4) Polymorphism in Korean Autoimmune Thyroid Disease

• Lee DK
• Kim YS
• Woo JT
• Kim SW
• Yang IM
• Kim JW
• Choi YK
• Paeng JR

Abstract

BACKGROUND
The cause of autoimmune thyroid diseases (AITD), including Graves disease and Hashimotos thyroiditis, is largely unknown. To identify the genes responsible, most attention has been focussed on the HLA regions in the early studies. However, these studies have repeatedly shown a weak association between AITD and the HLA-DR3 in Caucasians. To understand and find out the mechanisms underlying the development of AITD, a search for non-HLA linked susceptibility genes is important. A recent study from American population have indicated an association between a polymorphism of CILA-4 gene and Graves disease. To clarify the relationship of the CTLA-4 polymorphism and AITD, the allele frequency of CTLA-4 gene from the patients with Graves disease and with Hashimotos thyroiditis in Korean papulation were analysed.
METHODS
The CTLA-4 exon 1 polymorphism (49, A/G) was analysed by PCR-based, RFLP (Restriction Fragment Length Polymorphism) from 92 women and 37 men with Graves disease and 50 women and 9 men with Hashimotos thyroiditis diagnosed. Also, 287 healthy controls including 155 women and 132 men with no clinical evidence or family history of thyroid disease were enrolled.
RESULTS
1) In the group of Graves disease, there was significantly more patients with alanine homozygote (GG) than in control group (P<0.0005, RR=1.40). However, there was not significant with threonine homozygote (AA) between two groups (P=0.052). In the group of Hashimotos thyroiditis, no significant differences were found between all homozygotes and heterozygote. 2) In the group of Graves disease, there were significantly more patients with alanine homozygote (GG) (P<0.0001, RR=1.85) and significantly fewer patients with threonine homozygote (AA) than in the group of Hashimoto's thyroiditis (P<0.005, RR 0.25).
CONCLUSION
Regardless of sex difference, alanine homozygote (GG) at exon 1 (codon 17) of CTLA-4 is associated with Graves disease in Korean population, which suggests genetic susceptibility is some role in the pathogenesis of Graves disease.

MeSH Terms

Alanine
Exons
Female
Gene Frequency
Genetic Predisposition to Disease
Graves Disease
Heterozygote
HLA-DR3 Antigen
Homozygote
Humans
Lymphocytes*
Male
Polymorphism, Restriction Fragment Length
Sex Characteristics
Threonine
Thyroid Diseases*
Thyroid Gland*
Thyroiditis
Alanine
HLA-DR3 Antigen
Threonine