Association of an A/C single nucleotide polymorphism in programmed cell death-ligand 1 gene with Graves' disease in Japanese patients.

Abstract

Objective: Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) inhibit T-cell proliferation and activation. This inhibition down-regulates the immune responses. The association of a PD-L1 polymorphism with Graves' disease (GD) was studied. Design: The association of an A/C polymorphism at position 8923 in PD-L1 intron 4 with GD was studied. Patients: The study included 327 GD patients and 192 controls, of which 252 GD patients were followed over 5-10 years. Measurements: PD-L1 intron 4 position 8923 A/C polymorphism was typed using the PCR-restriction fragment length polymorphism method. Results: The A/C genotype frequencies were significantly different between GD patients and controls. The A/C and C/C frequencies were higher in GD patients than in controls. The A/A frequencies were lower in GD patients than in controls. C-allele frequency was higher in GD patients than in controls. A total of 252 GD patients were followed over 5-10 years; 200 had discontinued antithyroid drugs (ATD) while 52 continued to take ATD. Of these 200, 176 continued to be in remission and 24 had relapsed into hyperthyroidism. Significant differences in the duration of positive TBII, positive thyroid-stimulating antibodies, and ATD treatment were noted between the patients in remission and those that had relapsed. Significant differences in the A-and C-allele frequencies were noted between the two. The C-allele frequency was higher in GD patients who did not achieve remission than in those who achieved remission.

Lack of an Association of PD-1 and Its Ligand Genes with Behcet's Disease in a Chinese Han Population

“…In this study, however, we did not find any association of PD-1 rs2227981 and rs10204525, PD-L1 rs197000 and PD-L2 rs7854303 SNPs with Behcet's disease. These results are in disagreement to those seen in other autoimmune diseases reported among different ethnic groups [16]–[27], [33], [34]. This may be explained by the fact that the etiology and pathogenesis of Behcet's disease may be different from other autoimmune diseases [3].…”

“…Our previous study has demonstrated that PD-1 rs2227981 may be negatively associated with the extraocular manifestations of Vogt-Koyanagi-Harada syndrome in a Chinese Han population [32]. Although the PD-L1 rs1970000 polymorphism locates in intron 4, which does not affect an amino acid substitution, it may be close to or within transcriptional factor-binding sites [23] and may thus influence the expression of the PD-L1 gene through modifying the binding affinity of transcriptional factors [34]. This polymorphism has been shown to be associated with GD in Japanese patients [34].…”

“…Although the PD-L1 rs1970000 polymorphism locates in intron 4, which does not affect an amino acid substitution, it may be close to or within transcriptional factor-binding sites [23] and may thus influence the expression of the PD-L1 gene through modifying the binding affinity of transcriptional factors [34]. This polymorphism has been shown to be associated with GD in Japanese patients [34]. PD-L2 rs7854303 C encodes a serine in the transmembrane region, while PD-L2 rs7854303 T encodes a phenylalanine.…”

“…However, only few studies have addressed the association of ligand genes of PD-1 , PD-L1 and PD-L2 , with autoimmune disease [23], [33], [34].…”

Clinical Impact of Single Nucleotide Polymorphism in PD-L1 on Response to Nivolumab for Advanced Non-Small-Cell Lung Cancer Patients

“…After baseline fluorescence measurements at 25 °C, the PCR protocol included a 10-min incubation at 95 °C, 40 cycles of denaturing at 92 °C for 15 s and annealing and extending at 60 °C for 1 min, and a final measurement of fluorescence at 60 °C. SNPs with previously described associations or putative functional effects were selected24252627283940414243.…”