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

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

doi:10.3389/fphar.2021.729890

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…The concentration of IL-1β in T1DM patients was significantly higher than that in healthy controls. Osman A. E. et al, 2021 [22] IL levels in T1DM were higher than controls. Tangjittipokin W. et al, 2021 [24] IL1B SNPs are associated with T1DM susceptibility.…”

Section: Discussionmentioning

confidence: 91%

“…IL-1 and its SNPs were investigated by Li J. et al [22], more specifically, the authors of the study measured the concentration of IL-1β, a pro-inflammatory cytokine, in the blood of patients with T1DM and healthy controls. They found that the concentration of IL-1β was significantly higher in patients with T1DM compared to healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…Hehenkamp P. et al, 2021[20] T1DM monocytes have impaired IL-7 response and lower IL-7R expression. * Kumar S. et al, 2021[21] IL-17A polymorphism was not associated with increased risk for CP in T1DM patients.Li J. et al, 2021[22]…”

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confidence: 99%

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Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

D’Agostino,

Valentini,

Dolci

2024

Children

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Diabetes can trigger an increase in cytokine levels leading to the production of C-reactive protein and fibrinogen. These molecules promote subclinical inflammation, causing the expression of adhesive molecules and endothelial dysfunction. Despite the lack of a comprehensive panel for single-nucleotide polymorphisms (SNPs) for interleukins associated with type 1 diabetes mellitus (T1DM), understanding the inflammatory role of SNPs is crucial because periodontitis, the sixth complication of diabetes, is influenced via these genetic variations. This review focuses on the interleukin levels in T1DM patients with and without periodontitis, with a particular focus on childhood and on SNPs when reported. A search of PubMed and Scopus identified 21 relevant studies from the past five years. Several ILs were analyzed, emphasizing that T1DM still needs to be thoroughly explored regarding an IL polymorphisms panel; however, the last five years have led to the increased independence of this condition, causing autonomous inflammatory effects, which require further investigation. The periodontitis and T1DM association in children and adolescents represents a severe gap in the literature that should be filled; this scarce presence of studies serves as motivation for further clinical research.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

D’Agostino,

Valentini,

Dolci

2024

Children

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“…Individuals with IA-2A tend to be younger, have lower fasting and stimulated C-peptide levels, and experience a shorter duration of symptoms. Some immune-associated variants, such as in IL27 , IFIH1 , and CTLA4 , have been linked to the presence of IA-2A [ 27 – 29 ]. However, there is significant variability in the rate of pancreatic β cell destruction, which may be caused by genetic susceptibility [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of SIRT1 gene single-nucleotide polymorphisms on susceptibility to type 1 diabetes in a Han Chinese population

Li,

Yang,

Xia

et al. 2023

J Endocrinol Invest

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Aims SIRT1 deficiency has been associated with diabetes, and a variant of the SIRT1 gene has been found to be involved in human autoimmune diabetes; however, it is unclear whether this genetic variation exists in Han Chinese with type 1 diabetes (T1D) and whether it contributes to development of T1D. Therefore, we aimed to explore the association of the SIRT1 gene single-nucleotide polymorphisms (SNPs) rs10997866 and rs3818292 in a Han Chinese population with T1D. Methods This study recruited 2653 unrelated Han Chinese individuals, of whom 1289 had T1D and 1364 were healthy controls. Allelic and genotypic distributions of SIRT1 polymorphisms (rs10997866 and rs3818292) were determined by MassARRAY. Basic characteristics, genotype and allele frequencies of selected SNPs were compared between the T1D patients and healthy controls. Further genotype–phenotype association analysis of the SNPs was performed on the T1D patients divided into three groups according to genotype. Statistical analyses included the chi-square test, Mann‒Whitney U test, Kruskal‒Wallis H test and logistic regression. Results The allelic (G vs. A) and genotypic (GA vs. AA) distributions of SIRT1 rs10997866 were significantly different in T1D patients and healthy controls (P = 0.039, P = 0.027), and rs10997866 was associated with T1D susceptibility under dominant, overdominant and additive models (P = 0.026, P = 0.030 and P = 0.027, respectively). Moreover, genotype–phenotype association analysis showed the GG genotype of rs10997866 and the GG genotype of rs3818292 to be associated with higher titers of IA-2A (P = 0.013 and P = 0.038, respectively). Conclusion SIRT1 rs10997866 is significantly associated with T1D susceptibility, with the minor allele G conferring a higher risk of T1D. Moreover, SIRT1 gene rs10997866 and rs3818292 correlate with the titer of IA-2A in Han Chinese individuals with T1D.

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“…Genetic susceptibility is likely to play a significant role in it. Several studies have identified correlations between immune-related variants and the positive rate of islet autoantibodies, such as IL27-IA2A, IFIH1-IA2A, IL2RA-GADA, IL1B-ZnT8A, and CTLA4-IA2A ( 15 , 42 , 43 ). Our results confirm an association between PRRC2A risk alleles and islet autoantibody positivity.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

et al. 2022

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ObjectivesN6-methyladenosine (m6A) is essential in the regulation of the immune system, but the role that its single nucleotide polymorphisms (SNPs) play in the pathogenesis of type 1 diabetes (T1D) remains unknown. This study demonstrated the association between genetic variants in m6A regulators and T1D risk based on a case-control study in a Chinese population.MethodsThe tagging SNPs in m6A regulators were genotyped in 1005 autoantibody-positive patients with T1D and 1257 controls using the Illumina Human OmniZhongHua-8 platform. Islet-specific autoantibodies were examined by radioimmunoprecipitation in all the patients. The mixed-meal glucose tolerance test was performed on 355 newly diagnosed patients to evaluate their residual islet function. The functional annotations for the identified SNPs were performed in silico. Using 102 samples from a whole-genome expression microarray, key signaling pathways associated with m6A regulators in T1D were comprehendingly evaluated.ResultsUnder the additive model, we observed three tag SNPs in the noncoding region of the PRRC2A (rs2260051, rs3130623) and YTHDC2 (rs1862315) gene are associated with T1D risk. Although no association was found between these SNPs and islet function, patients carrying risk variants had a higher positive rate for ZnT8A, GADA, and IA-2A. Further analyses showed that rs2260051[T] was associated with increased expression of PRRC2A mRNA (P = 7.0E-13), and PRRC2A mRNA was significantly higher in peripheral blood mononuclear cell samples from patients with T1D compared to normal samples (P = 0.022). Enrichment analyses indicated that increased PRRC2A expression engages in the most significant hallmarks of cytokine-cytokine receptor interaction, cell adhesion and chemotaxis, and neurotransmitter regulation pathways. The potential role of increased PRRC2A in disrupting immune homeostasis is through the PI3K/AKT pathway and neuro-immune interactions.ConclusionThis study found intronic variants in PRRC2A and YTHDC2 associated with T1D risk in a Chinese Han population. PRRC2A rs2260051[T] may be implicated in unbalanced immune homeostasis by affecting the expression of PRRC2A mRNA. These findings enriched our understanding of m6A regulators and their intronic SNPs that underlie the pathogenesis of T1D.

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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

Cited by 6 publications

References 35 publications

Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

Exploring Interleukin Levels in Type 1 Diabetes and Periodontitis: A Review with a Focus on Childhood

Effect of SIRT1 gene single-nucleotide polymorphisms on susceptibility to type 1 diabetes in a Han Chinese population

Genome-Wide Identification of N6-Methyladenosine Associated SNPs as Potential Functional Variants for Type 1 Diabetes

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