Arafa Roshdan M, Desouky Somaya M, Emam Sherin M, Abed Neveen Tawfik, Mohamed Sahar Y
Egypt J Immunol. 2015;22(1):49-57.
Type 1 diabetes is one of the most common chronic childhood illnesses. Interplay between genetic susceptibility and environmental factors is thought to provide the fundamental element for the disease. It has been shown that more than 40 genetic loci are associated with T1DM. Important one among these is the CTLA-4. This work aimed to detect Cytotoxic T Lymphocyte-associated antigen 4 (CTLA-4) gene polymorphism in patients with type 1 diabetes mellitus T1DM using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to clarify its role in the susceptibility to T1DM. The study was carried out on forty unrelated Egyptian children with TIDM. Twenty unrelated healthy children were enrolled as a control group. Blood samples were collected from patients and control groups and subjected to CTLA-4 gene polymorphism analysis using polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). CTLA-4 G allele and GG homozygous genotype were significantly increased in T1DM patients than in control group (P < 0.001, P = 0.002 respectively). There was significant association between the three CTLA-4 genotypes (AA, AG, GG) and diabetic complications (p = 0.002), AG and GG polymorphisms were associated with complications of diabetes with ratio 84.6% and 100% respectively. While no association was found with sex, weight, height, risk factors of diabetes or insulin treatment. It was concluded that there is a strong association between AG polymorphism and T1DM (P = 0.002).
1型糖尿病是儿童期最常见的慢性疾病之一。遗传易感性与环境因素之间的相互作用被认为是该疾病的基本要素。已有研究表明，超过40个基因位点与1型糖尿病（T1DM）相关。其中重要的一个是细胞毒性T淋巴细胞相关抗原4（CTLA-4）。本研究旨在利用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测1型糖尿病（T1DM）患者的细胞毒性T淋巴细胞相关抗原4（CTLA-4）基因多态性，以阐明其在T1DM易感性中的作用。本研究对40名无亲缘关系的埃及T1DM儿童进行。招募20名无亲缘关系的健康儿童作为对照组。采集患者和对照组的血样，采用聚合酶链反应随后进行限制性片段长度多态性（PCR-RFLP）分析CTLA-4基因多态性。与对照组相比，T1DM患者的CTLA-4 G等位基因和GG纯合基因型显著增加（分别为P < 0.001，P = 0.002）。CTLA-4三种基因型（AA、AG、GG）与糖尿病并发症之间存在显著关联（p = 0.002），AG和GG多态性分别与糖尿病并发症相关，比例分别为84.6%和100%。而未发现与性别、体重、身高、糖尿病危险因素或胰岛素治疗有关联。研究得出结论，AG多态性与T1DM之间存在强关联（P = 0.002）。
