Methylation profile of CD247 and FOXP3 genes and frequency of certain HLA-DQ haplotypes in Celiac disease

IF 2.6 4区医学 Q2 GASTROENTEROLOGY & HEPATOLOGY

Clinics and research in hepatology and gastroenterology Pub Date : 2025-02-24 DOI:10.1016/j.clinre.2025.102562

Malik Ejder Yildirim , Hilmi Ataseven , Hande Kucuk Kurtulgan , Seyma Tastemur , Ahmet Sirin

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引用次数: 0

Abstract

Background

Celiac disease is an autoimmune disorder that affects the small intestine in people with gluten intolerance. HLA-DQ2 and DQ8 have been associated with Celiac Disease. CD247 is a subunit of the T cell receptor complex and Forkhead box P3 (FOXP3) is a transcription factor involved in the regulation of the immune response. Expression levels of these two markers in various diseases, including autoimmune disorders, are controversial. In this context, we aimed to shed light on the etiopathogenesis of Celiac disease by determining the methylation profile of CD247 and FOXP3 genes, and to calculate the frequency of HLA-DQ haplotypes in this disease.

Methods

Methylated and unmethylated copy numbers of the CD247 and FOXP3 genes in samples were calculated using the methylation-specific qPCR method. The records regarding HLA-DQ2 and DQ8 genotypes previously detected from our patients by Real Time PCR and tissue transglutaminase IgA (TTG-IgA) by ELISA, were analyzed.

Results

CD247 methylation rate in our patients was significantly lower than in controls. According to the Marsh classification, the methylation level in Marsh type 2–3 patients was statistically lower than in type 1. On the contrary, FOXP3 had a significantly higher methylation rate in the patient group compared to healthy controls, and this gene was also found to be more methylated in Marsh type 2–3 patients than in Marsh type 1. In the patient group, HLA-DQ2 positivity was 82.5% and HLA-DQ8 positivity was 37.5%.

Conclusion

The data suggest that CD247 expression is upregulated, whereas FOXP3 expression is downregulated in Celiac disease. Among HLA haplotypes, HLA-DQ2 heterodimer came to the forefront with its frequency in terms of celiac predisposition.

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乳糜泻中CD247和FOXP3基因的甲基化谱和某些HLA-DQ单倍型的频率

背景：乳糜泻是一种自身免疫性疾病，影响麸质不耐症患者的小肠。HLA-DQ2和DQ8与乳糜泻有关。CD247是T细胞受体复合物的一个亚基，叉头盒P3 （FOXP3）是一种参与免疫反应调节的转录因子。这两种标志物在包括自身免疫性疾病在内的各种疾病中的表达水平存在争议。在这种情况下，我们旨在通过确定CD247和FOXP3基因的甲基化谱，并计算HLA-DQ单倍型在乳糜泻中的频率来阐明乳糜泻的发病机制。方法：采用甲基化特异性qPCR方法计算样本中CD247和FOXP3基因的甲基化和非甲基化拷贝数。分析本组患者采用Real Time PCR检测的HLA-DQ2和DQ8基因型和ELISA检测的组织转谷氨酰胺酶IgA （TTG-IgA）基因型的记录。结果：我们患者的CD247甲基化率明显低于对照组。根据Marsh分类，2-3型患者的甲基化水平在统计学上低于1型患者。相反，与健康对照组相比，患者组FOXP3的甲基化率明显更高，并且该基因在Marsh 2-3型患者中的甲基化程度也高于Marsh 1型患者。患者组HLA-DQ2阳性率为82.5%，HLA-DQ8阳性率为37.5%。结论：CD247在乳糜泻中表达上调，而FOXP3表达下调。在HLA单倍型中，HLA- dq2异源二聚体以其在乳糜泻易感性方面的频率居首位。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinics and research in hepatology and gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

4.30

自引率

3.70%

发文量

198

审稿时长

42 days

期刊介绍： Clinics and Research in Hepatology and Gastroenterology publishes high-quality original research papers in the field of hepatology and gastroenterology. The editors put the accent on rapid communication of new research and clinical developments and so called "hot topic" issues. Following a clear Editorial line, besides original articles and case reports, each issue features editorials, commentaries and reviews. The journal encourages research and discussion between all those involved in the specialty on an international level. All articles are peer reviewed by international experts, the articles in press are online and indexed in the international databases (Current Contents, Pubmed, Scopus, Science Direct). Clinics and Research in Hepatology and Gastroenterology is a subscription journal (with optional open access), which allows you to publish your research without any cost to you (unless you proactively chose the open access option). Your article will be available to all researchers around the globe whose institution has a subscription to the journal.