Association of PD-1 and PD-L1 Genetic Polymorphyisms with Type 1 Diabetes Susceptibility.

Chenyue Qian,Jie Pan,Aiming Shi,Xiaohong Chen,Chen Fang,Xin Wang,Sicheng Li,Heming Guo

doi:10.1155/2018/1614683

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]

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

Methods

Results

Conclusion