Abstract

Aims The programmed death- (PD-) 1/PD-1 ligand (PD-L) pathway plays an important role in regulating T cell activation and maintaining peripheral tolerance. Accumulated studies showed that PD-1/PD-L1 pathway was involved in the development of type 1 diabetes (T1DM). Since the genetic background of type 1 diabetes differs greatly among the different population, we aim to investigate the association of genetic polymorphisms in PD-1 and PD-L1 with T1DM susceptibility in Chinese population. Methods In total, 166 T1DM patients and 100 healthy controls were enrolled into the study. Genomic DNA was extracted from 4 mL peripheral blood samples collected from each subject. Genotyping of 8 selected SNPs of PD-1 and PD-L1 was carried out by the pyrosequencing PSQ 24 System using PyroMark Gold reagents (QIAGEN). Results SNP rs4143815 in PD-L1 was significantly associated with T1DM. People carrying the C allele of rs4143815 suffering less risk of T1DM and T1DM patients with G/G genotype showed higher levels of autoantibody (AAB) positive incidence compared with C allele carriers. No significant associations were found in other SNPs. Conclusions Our results indicate that rs4143815 of PD-L1 is significantly associated with T1DM and may serve as a new biomarker to predict the T1DM susceptibility.

Highlights

  • The increased prevalence of diabetes mellitus is considered one of the greatest public health challenges nowadays

  • Accumulated studies showed that blockage of the interaction between programmed death- (PD-)1 and Programmed death ligand-1 (PD-L1) can help with better prognosis in various malignant tumors [6, 9, 10]

  • PD-L1 recently had been found expressed in the islets of people with type 1 diabetes [20], and we found that PD-L1 was significantly reduced in the serum of Type 1 diabetes mellitus (T1DM) patients [21]

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Summary

Introduction

The increased prevalence of diabetes mellitus is considered one of the greatest public health challenges nowadays. Type 1 diabetes mellitus (T1DM), a polygenic autoimmune disease, is resulted from both genetic and environmental factors [1]. Programmed cell death 1 (PD-1) is an immunoinhibitory factor belonging to the CD28/B7 family. It plays a vital role in regulating T cell activation and maintaining peripheral tolerance as a core costimulatory molecule [2, 3]. Programmed death ligand-1 (PD-L1) has been shown to be overexpressed in many cancers, including gastric cancer [7], esophageal cancer, pancreatic cancer, and other human gastrointestinal tumors [8]. Autoimmune diabetes has been reported after receiving anti-PD-1 therapy for tumor in both mouse models and human cases [11,12,13]. We assume that there may be a connection between PD-1/PD-L1 pathway and autoimmune diabetes

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