Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study

Abstract

Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21–1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15–1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27–2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22–2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D’ = 0.92). 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.

Identification of susceptibility SNPs in CTLA-4 and PTPN22 for scleritis in Han Chinese

“…Previous studies also found that the G allele and GG genotype were risk factors for several immune-mediated diseases, such as RA [14], IBD [16], T1D [24], AS [20] and GD [22]. Previous studies also found that the G allele and GG genotype were risk factors for several immune-mediated diseases, such as RA [14], IBD [16], T1D [24], AS [20] and GD [22].…”

“…CD28, which is a co-stimulatory molecule, together with B7-1 and B7-2 antigens, activates T cells. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) also serves as a negative factor on TCR signaling [12]. Protein tyrosine phosphatase non-receptor type 22 (PTPN22) also serves as a negative factor on TCR signaling [12].…”

“…Protein tyrosine phosphatase non-receptor type 22 (PTPN22) also serves as a negative factor on TCR signaling [12]. A number of studies have shown that several SNPs of CTLA4 and PTPN22 are associated with a number of systemic autoimmune diseases, such as rheumatoid arthritis (RA) [14,15], inflammatory bowel disease (IBD) [16,17], systemic lupus erythematosus (SLE) [18,19], ankylosing spondylitis (AS) [20,21], Graves' disease (GD) [22,23], type 1 diabetes (T1D) [24][25][26], alopecia areata [27,28] and psoriatic arthritis [29]. A number of studies have shown that several SNPs of CTLA4 and PTPN22 are associated with a number of systemic autoimmune diseases, such as rheumatoid arthritis (RA) [14,15], inflammatory bowel disease (IBD) [16,17], systemic lupus erythematosus (SLE) [18,19], ankylosing spondylitis (AS) [20,21], Graves' disease (GD) [22,23], type 1 diabetes (T1D) [24][25][26], alopecia areata [27,28] and psoriatic arthritis [29].…”

Recombinant adenovirus expressing a dendritic cell‑targeted melanoma surface antigen for tumor‑specific immunotherapy in melanoma mice model

“…Then, inactivated B16-F10 cells (1x10 6 ) were incubated with splenocytes (1x10 4 ) for 12 h at 37˚C. Release of interferon (IFN) was evaluated by ELISA (DY485, Bio-Rad Laboratories, Inc., Hercules, CA, USA) in the supernatants following culture for 72 h. T cells (1x10 6 ) from the splenocytes were purified, as previously described (32) and co-cultured with fresh DMEM B16-F10 cells for 4 h at 37˚C at the effector, at target ratios of 5:1, 20:1 and 40:1, which were ratios used in a previous study (42). Specific CTL activity to the target cells was determined by MTT cytotoxicity assays, as previously described (43).…”

Association of candidate gene polymorphisms for autoimmune thyroid diseases in patients with familial diffuse toxic goiter and autoimmune thyroiditis

“…лых пациентов с ДТЗ и среди аналогичного количе-ства детей с данным заболеванием. Авторы так же, как и в настоящем исследовании, не выявили су-щественных различий между пациентами старшей и младшей возрастных групп [16]. Ген PTPN22 кодирует лимфоцитарную тирозин-фосфатазу, которая является отрицательным регуля-тором Т-клеточной активации.…”