CTLA-4 AG genotype had an eightfold (OR: 8.050; 95% CI: 2.87-22.5; p = 0.0001) and GG genotype had a sevenfold (OR: 7.025; 95% CI: 1.67-29.4; p = 0.007) increase in the risk of recurrence in the patients with GD.
We investigated two major genetic susceptibility loci for Graves' disease in ophthalmopathy; the MHC class II region and the cytotoxic T lymphocyte antigen-4 (CTLA4) gene.
The recently described single nucleotide polymorphism CT60, located in the 3' untranslated region of CTLA4 is associated with Graves' disease, thyroiditis, autoimmune diabetes and other autoimmune diseases.
In patients with untreated GD there was a statistically significant positive correlation between the expression of CTLA-4 on the surface of peripheral blood T cells and the index of TSAb antibodies (R = 0.54, p < 0.001) as well as a negative correlation with TBAb antibody titer (R = -0.58, p < 0.001).
's association study of CTLA4 and Graves disease, showing how it can be used to dissect the association signal, giving potentially interesting results of allelic heterogeneity and interaction.
In contrast to a single gene effect, we observed that interactions between the HLADRB1/PTPN22 and HLADRB1/CTLA4 genes more closely predicted the risk of GD onset in young patients.
In this study, associations of five CTLA4 single nucleotide polymorphisms (-1722A/G, -1661A/G, -318C/T, +49G/A, CT60) with GD risk and GO susceptibility in GD patients were investigated in a Chinese population.
The study of this family allowed us to: (1) reinforce a number of reports on linkage and association of the CTLA4 region to T1D and AITD; (2) demonstrate that a single haplotypic variant in this region constitutes an etiological factor to disease susceptibility in T1D, GD and HT; (3) reveal a strong genetic interaction of the CTLA4 and HLA loci in the genetic architecture of autoimmune disease; (4) emphasise the value of large pedigrees drawn from isolated populations as tools to single out the effect of individual loci in the etiology of complex diseases.
CTLA4 gene and Graves' disease: association of Graves' disease with the CTLA4 exon 1 and intron 1 polymorphisms, but not with the promoter polymorphism.
The purpose of this study was to investigate the relationships between GD and single nucleotide polymorphisms (SNPs) from CTLA-4, PTPN22, PTPN12, FCRL3 (general autoimmunity genes regulating T and B cells) and the TSHR and Tg genes (disease-specific genes).
These results support the concept that CTLA-4 plays a critical role in the autoimmune process in GD, and that GD depends on multiple genetic susceptibility factors.
We also found the HLA-DRB1*03 allele to be associated with GD; interestingly, the association of the CTLA-4 markers was independent from the HLA DRB1*03 status.
At present three loci, namely human leukocyte antigen (HLA, 6p21.3), cytotoxic T-lymphocyte-associated esterase-4 (CTLA4, 2q33), and thyroid-stimulating hormone receptor (TSHR, 14q31), are the only well-known genetic determinants for Graves disease.
The difference in the association between GD and AA suggests that the CTLA4 and TSHR are not main factors contributing to determining common genetic basis among GD and AA.
In addition to the HLA region, cytotoxic T lymphocyte-associated molecule-4 (CTLA4) gene polymorphisms +49G>A and +6230G>A (CT60) were positively associated with GD.
The aim was to generate large-scale evidence on whether the CTLA-4 polymorphisms (A49G and CT60) and haplotypes thereof increase the susceptibility to GD and/or HT.
These were negative except for the HLA and CTLA-4 genes, which were found to be weakly associated with GO giving similar relative risk (RR) as in GD patients without ophthalmopathy.
Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.
Association of Graves' disease and Graves' ophthalmopathy with the polymorphisms in promoter and exon 1 of cytotoxic T lymphocyte associated antigen-4 gene.
We conclude that the CTLA4 + 49 A/G and CT 60 A/G SNPs have a significant association with the risk of GD development in Kashmiri population and CTLA4 mRNA expression is significantly decreased in GD.