The Positivity Rate of IA-2A and ZnT8A in the Chinese Han Population With Type 1 Diabetes Mellitus: Association With rs1143627 and rs1143643 Polymorphisms in the IL1B Gene.

Jiaqi Li,Gan Huang,Haibo Yu,Jian Lin,Xiaoxiao Sun,Xia Li,Yang Xiao,Zhiguo Xie,Shuoming Luo,Zhiguang Zhou

doi:10.3389/fphar.2021.729890

Abstract

Objective: To investigate the association between susceptibility to type 1 diabetes mellitus (T1DM) and polymorphisms (rs1143627 and rs1143643) in the interleukin 1 beta (IL1B) gene in the Chinese Han population. Methods: The Meso Scale Discovery (MSD) method was used to detect the concentration of IL-1β in 24 T1DM patients and 27 healthy controls. MassARRAY was used to analyze the polymorphisms in the IL1B gene in 510 patients with classic T1DM and 531 healthy controls. The general data of the T1DM patients and healthy controls were compared by the chi-square test and Mann-Whitney U test. The chi-square test and logistic regression were used to analyze the frequency distributions of alleles and genotypes of polymorphisms in the IL1B gene. The Kruskal-Wallis H test and chi-square test were used for the genotype-phenotype analysis of rs1143627 and rs1143643 in the IL1B gene. Results: ① The concentration of IL-1β in T1DM patients was significantly higher than that in healthy controls. ② rs1143627 and rs1143643 in the IL1B gene were significantly correlated with the positivity rates for IA-2A and ZnT8A; genotype GG at rs1143627 and genotype CC at rs1143643 in the case group showed lower positivity rates for IA-2A and ZnT8A. ③ There was no significant difference in the genotypes or allele frequencies at rs1143627 (GG/GA/AA) or rs1143643 (CC/CT/TT) between the case group and control group (p > 0.05). ④ rs1143627 and rs1143643 were not found to be linked to T1DM susceptibility under different genetic models. Conclusion: rs1143627 and rs1143643 in the IL1B gene correlate with the positivity rate of IA-2A and ZnT8A in Chinese Han individuals with T1DM.

Highlights

Type 1 diabetes mellitus (T1DM), an organ-specific chronic autoimmune disease, is characterized by insulin deficiency and the resultant hyperglycemia caused by the selective destruction of pancreatic beta cells mediated by T lymphocytes
1 The concentration of IL-1β in T1DM patients was significantly higher than that in healthy controls. 2 rs1143627 and rs1143643 in the interleukin 1 beta (IL1B) gene were significantly correlated with the positivity rates for IA-2A and ZnT8A; genotype GG at rs1143627 and genotype CC at rs1143643 in the case group showed lower positivity rates for IA-2A and ZnT8A. 3 There was no significant difference in the genotypes or allele frequencies at rs1143627 (GG/GA/AA) or rs1143643 (CC/CT/TT) between the case group and control group (p > 0.05). 4 rs1143627 and rs1143643 were not found to be linked to T1DM susceptibility under different genetic models
In addition to the HLA gene family, genome-wide association studies (GWAS) have identified over 60 non-HLA genes related to the risk of T1DM, and these genes participate in the inheritance of T1DM with small genetic effects through their various combinations (Noble, 2015)

Summary

Introduction

Type 1 diabetes mellitus (T1DM), an organ-specific chronic autoimmune disease, is characterized by insulin deficiency and the resultant hyperglycemia caused by the selective destruction of pancreatic beta cells mediated by T lymphocytes. Genetic and environmental factors contribute to the development and progression of T1DM (DiMeglio et al, 2018; Xie et al, 2018). Knowledge of T1DM, including its epidemiology, genetics, immune response, beta cell phenotypes, and disease therapy, has greatly increased. The understanding of T1DM pathogenesis is not very clear. The pathogenesis and potential directions for future research on T1DM still need to be explored (Skyler, 2018). T1DM is a disease of polygenic inheritance with strong genetic susceptibility (Pociot and Lernmark, 2016). In addition to the HLA gene family, genome-wide association studies (GWAS) have identified over 60 non-HLA genes related to the risk of T1DM, and these genes participate in the inheritance of T1DM with small genetic effects through their various combinations (Noble, 2015)

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Conclusion