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DNA methylation and mRNA expression of HLA-DQA1 alleles in type 1 diabetes mellitus

机译:1型糖尿病患者HLA-DQA1等位基因的DNA甲基化和mRNA表达

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摘要

Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with human leucocyte antigen (HLA) class II genes, including HLA-DQA1 gene. Our aim was to investigate DNA methylation of HLA-DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA-DQA1 allele expression of patients with T1D and healthy controls. DNA methylation is one of the epigenetic modifications that regulate gene expression and is known to be shaped by the environment. Sixty one patients with T1D and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulphite and HLA-DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA-DQA1 promoter alleles was analysed. Individual mRNA HLA-DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA-DQA1 allele 02:01 expression (PPIA normalization, P-corr = 0.041; DRA normalization, P-corr = 0.052) between healthy controls and patients with T1D. The complete methylation profile of the HLA-DQA1 promoter was gained with the most methylated allele DQA1(star)02:01 and the least methylated DQA1(star)05:01 in both studied groups. Methylation profile observed in patients with T1D and healthy controls was similar, and no correlation between HLA-DQA1 allele expression and DNA methylation was found. Although we have not proved significant methylation differences between the two groups, detailed DNA methylation status and its correlation with expression of each HLA-DQA1 allele in patients with T1D have been described for the first time.
机译:1型糖尿病(T1D)属于多基因多因素自身免疫性疾病。最高风险与人类白细胞抗原(HLA)II类基因(包括HLA-DQA1基因)相关。我们的目的是调查HLA-DQA1启动子等位基因(QAP)的DNA甲基化,并将甲基化状态与T1D患者和健康对照组的个体HLA-DQA1等位基因表达相关。 DNA甲基化是调节基因表达的表观遗传修饰之一,已知受环境影响。本研究涉及61位T1D患者和39位健康对照。用亚硫酸氢钠处理分离的DNA,并使用巢式PCR扩增HLA-DQA1启动子序列。测序后,分析了HLA-DQA1启动子等位基因的DNA甲基化。使用两个不同的内源性对照(PPIA,DRA)评估了单个mRNA HLA-DQA1相对等位基因的表达。我们发现健康对照与T1D患者之间HLA-DQA1等位基因02:01表达有统计学显着差异(PPIA标准化,P-corr = 0.041; DRA标准化,P-corr = 0.052)。在两个研究组中,甲基化程度最高的等位基因DQA1(star)02:01和甲基化程度最低的DQA1(star)05:01获得了HLA-DQA1启动子的完整甲基化谱。在T1D患者和健康对照者中观察到的甲基化分布相似,并且未发现HLA-DQA1等位基因表达与DNA甲基化之间存在相关性。尽管我们尚未证明两组之间存在明显的甲基化差异,但首次描述了T1D患者的详细DNA甲基化状态及其与每个HLA-DQA1等位基因表达的相关性。

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