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Association of an A/C single nucleotide polymorphism in programmed cell death-ligand 1 (PD-L1) gene with Graves' disease in Japanese patients

M Hayashi, Department of Endocrinology and Metabolism, University of the Ryukyus School of Medicine, Nishihara, Japan
T Kouki, Department of Endocrinology and Metabolism, University of the Ryukyus School of Medicine , Nishihara, 9030215, Japan
N Takasu, Department of Endocrinology and Metabolism, University of the Ryukyus School of Medicine, Nishihara, Japan
S Sunagawa, Department of Endocrinology and Metabolism, University of the Ryukyus School of Medicine, Nishihara, Japan
I Komiya, Department of Endocrinology and Metabolism, University of the Ryukyus School of Medicine, Nishihara, Japan

Correspondence: Tsuyoshi Kouki, Email: tkouki{at}ryudai2nai.com

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: Association of an A/C polymorphism at position 8923 in PD-L1 with GD was studied.

Patients: 327 GD-patients and 192 controls were studied. 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 frequency was lower in GD-patients than in controls. C-allele frequency was higher in GD-patients than in controls. 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 TSAb, and ATD-treatment were noted between the patients in remission and those that had relapsed. Significant differences in the A, 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.

Conclusion: An A/C polymorphism at position 8923 in PD-L1 is associated with GD. The PD-L1 polymorphism plays a role in GD-development. GD-patients with the C allele at position 8923 in PD-L1 gene had difficulty in achieving remission.