Indian Journal of Clinical Biochemistry, 2005, 20 (1) 9-17

AUTOIMMUNE THYROID DISORDERS - AN UPDATE

Manorama Swain*, Truptirekha Swain** and Binoy Kumar Mohanty***

The cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene,

encoding a negative regulator of the T-lymphocyte

immune response, had been reported to be associated

and/or linked to AITD. Recently, AITD susceptibility in

the Caucasians was mapped to the 6.1-KB3’UTR of

the CTLA-4 gene, in which the three single nucleotide

polymorphisms (SNPs) CT60, JO31, and JO30 were

strongly associated with AITD. The SNP, JO31 was

most significantly associated with AITD in the

Japanese, whereas the association of the JO30 with

AITD was not observed (11). Ueda H & coworkers have

identified polymorphism of CTLA-4 gene that is a

candidate gene for common autoimmune disorders

like GD, AH and Type-1 Diabetes (TID). The disease

susceptibility was mapped to a non-coding 6.1 KB 3|

region of CTLA-4, the common allelic variation of which

was correlated with lower mRNA levels of the soluble

alternative splice form of CTLA-4 (12). It was recently

shown, that 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, was

associated with the relapse of the hyperthyroidism after

antithyroid withdrawal. 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 (13).

11. Furugaki K. Shirasawa S, Ishikawa N, Ito K,

Kobota S, Kuma K, Tamai H, Akamizu T, Hiratani

H, Tanaka M, Sasazuki T, (2004) Association of

the T-cell regulatory gene CTLA4 with Graves’

disease and autoimmune thyroid disease in the

Japanese. J. Hum. Genet. 49 (3),166-8.

12. Ueda, H., Howson, J.M., Esposito, L., (2003)

Association of the T-Cell regulatory gene CTLA-4

with susceptibility to autoimmune disease.

Nature, May 29. 423(6939), 506-11.

13. Pei-Win Wang, Rue-Tsuan Liu, Suh-Hang Hank

Juo et al,(2004) Cytotoxic T Lymphocyte-

Associated Molecule-4 Polymorphism and

Relapse of Graves’ Hyperthyroidism after

Antithyroid withdrawal, The J. Clin. Endocrinol.

Metab. Vol.8 No.1, 169-173.