Investigating polymorphisms in genes encoding TGF-β1, IL-10, and IL-6 and their associations with type 1 diabetes mellitus

Alghamdi Ahmed H, El-Refaei Mohamed F, Shatla Ibrahim M, El-Sherbini Sherif M
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Abstract

Many cytokines play a role in the pathogenesis of Type 1 Diabetes (T1D), and gene polymorphisms could possibly contribute to the disease’s genetic predisposition because they can affect cytokine production or function. The purpose of this study was to investigate the role of the gene polymorphisms TGF-β1 (+869T/C), (+915G/C), IL-10 {-1082 G/A), (-819 C/T), and (-592 A/C), and IL-6 (-174 G/C) in hereditary vulnerability to T1D. The Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP) was used to analyze the polymorphisms. According to their genotypes, individuals were divided into the low-, high-, or intermediate-producer phenotypes predicted for these cytokines polymorphisms. Our findings revealed that the production of TGF-β1 was significantly higher in control than in T1D participants whereas the IL-6 genotype with low IL-6 production was significantly increased in the cases compared to the control. A significant association was evident between TGF-β1 and IL-6 low production and the incidence of T1D, thereby confirming the importance of TGF-β1 and IL-6 polymorphism as a genetic factor contributing to the incidence of T1D. By contrast, the involvement of IL-10 in the incidence of T1D was not as clear. Although some evidence supports a relationship, no statistically significant association has been verified between IL-10 and T1D. This type of measurement could be beneficial in determining the susceptibility and severity of the T1D condition while also taking into consideration the prediction of T1D incidence.
TGF-β1、IL-10和IL-6编码基因多态性及其与1型糖尿病的关系研究
许多细胞因子在1型糖尿病(T1D)的发病机制中发挥作用,基因多态性可能有助于该疾病的遗传易感性,因为它们可以影响细胞因子的产生或功能。本研究旨在探讨TGF-β1 (+869T/C)、(+915G/C)、IL-10 (-1082 G/A)、(-819 C/T)、(-592 A/C)和IL-6 (-174 G/C)基因多态性在T1D遗传易感性中的作用。采用序列特异性引物聚合酶链反应(PCR-SSP)分析多态性。根据他们的基因型,个体被分为预测这些细胞因子多态性的低、高或中等生产者表型。我们的研究结果显示,对照组TGF-β1的产生明显高于T1D参与者,而IL-6基因型低IL-6产生的病例与对照组相比显著增加。TGF-β1和IL-6低生成与T1D的发生有显著的相关性,从而证实TGF-β1和IL-6多态性作为T1D发生的遗传因素的重要性。相比之下,IL-10在T1D发病中的作用尚不清楚。虽然一些证据支持这种关系,但IL-10和T1D之间没有统计学上显著的关联。这种类型的测量有助于确定T1D病情的易感性和严重程度,同时也考虑到T1D发病率的预测。
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