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Association of PD-1 gene polymorphisms and serum soluble PD-1 levels with type 1 diabetes mellitus susceptibility in a Chinese Han cohort: a case-control study.

Frontiers in immunology 2026 Vol.17() p. 1783770

Zhao R, Feng X, Wang N, Wang Z, Liu J, Wang G

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[BACKGROUND] The programmed cell death 1 (PD-1)/PD-L1 pathway plays a critical role in immune tolerance and has been implicated in type 1 diabetes mellitus (T1DM).

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  • OR 0.160

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BibTeX ↓ RIS ↓
APA Zhao R, Feng X, et al. (2026). Association of PD-1 gene polymorphisms and serum soluble PD-1 levels with type 1 diabetes mellitus susceptibility in a Chinese Han cohort: a case-control study.. Frontiers in immunology, 17, 1783770. https://doi.org/10.3389/fimmu.2026.1783770
MLA Zhao R, et al.. "Association of PD-1 gene polymorphisms and serum soluble PD-1 levels with type 1 diabetes mellitus susceptibility in a Chinese Han cohort: a case-control study.." Frontiers in immunology, vol. 17, 2026, pp. 1783770.
PMID 41972147

Abstract

[BACKGROUND] The programmed cell death 1 (PD-1)/PD-L1 pathway plays a critical role in immune tolerance and has been implicated in type 1 diabetes mellitus (T1DM). However, the associations between PD-1 polymorphisms, circulating soluble PD-1 (sPD-1), and T1DM susceptibility remain unclear in Chinese populations. This study evaluated the relationships of PD-1 rs2227981 and rs2227982 variants and serum sPD-1 levels with T1DM risk.

[METHODS] 89 T1DM patients and 70 healthy controls were enrolled. Genotyping was performed using TaqMan assays. Serum sPD-1 levels were measured by enzyme linked immunosorbent assay (ELISA) in a subset (44 T1DM, 28 controls). Genetic associations were assessed using multivariable logistic regression adjusting for sex, age, uric acid (UA), and triglycerides (TG).

[RESULTS] Significant differences in allele and genotype distributions of rs2227981 and rs2227982 were observed between groups. After adjustment, rs2227981 was significantly associated with T1DM under recessive (adjusted OR = 0.160,  = 0.027) and codominant models (adjusted OR = 6.764,  = 0.024). Rs2227982 remained significantly associated under additive (adjusted OR = 1.770,  = 0.012), dominant (adjusted OR = 0.454,  = 0.039), recessive (adjusted OR = 0.449, = 0.032), and codominant models (adjusted OR = 0.319,  = 0.012). In genotype-phenotype analysis, rs2227982 was associated with HbA1c levels ( = 0.036). Serum sPD-1 concentrations were elevated in T1DM patients ( = 0.013) but showed no correlation with glycemic parameters, autoantibody status, or PD-1 genotypes.

[CONCLUSIONS] PD-1 rs2227981 and rs2227982 polymorphisms are associated with T1DM susceptibility in a Chinese Han cohort. Rs2227982 may be linked to glycemic phenotype, while elevated sPD-1 levels suggest altered immune checkpoint regulation rather than reflecting short-term metabolic control. Larger and longitudinal studies are needed to confirm these findings.

MeSH Terms

Humans; Diabetes Mellitus, Type 1; Programmed Cell Death 1 Receptor; Male; Female; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Adult; Case-Control Studies; China; Asian People; Genotype; Genetic Association Studies; Young Adult; Alleles; Middle Aged; East Asian People

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