Cellular and Molecular Research Center, Zahedan University of Medical Sciences, Zahedan, Iran.
Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Postgrad Med J. 2017 Dec;93(1106):758-761. doi: 10.1136/postgradmedj-2017-134851. Epub 2017 Jul 4.
In patients with systemic lupus erythematosus (SLE), loss of immunological tolerance to self-nuclear antigens and abnormal activation of self-reactive T and B cells lead to self-antibodies and immune complex production. The autoreactive lymphocytes are removed by the apoptotic process in healthy individuals; however, apoptosis disruption could cause accumulation of apoptotic bodies and nuclear debris. Therefore, apoptosis plays a crucial role in the pathogenesis of autoimmune diseases.
To investigate the association between two polymorphisms in an apoptotic-related gene, MDM2, and SLE.
A case-control study was conducted on 200 patients with SLE and 206 healthy volunteers matched for age, sex, and ethnicity. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR methods were used for genotyping.
No association was found between the MDM2 T309G polymorphism (rs2279744) and SLE. The ID genotype of the insertion/deletion (I/D) polymorphism (rs3730485) was significantly lower in patients with SLE, and the ID genotype could be a protective factor for SLE. The DD genotype was not associated with SLE. The frequency of combined TT/ID and GG/ID genotypes of MDM2 T309G and I/D polymorphisms was lower in the patients with SLE and was associated with a lower risk of SLE. The frequency of the TD haplotype of MDM2 T309G and I/D polymorphisms was significantly lower in patients with SLE and could reduce the SLE risk.
The ID genotype of the MDM2 I/D polymorphism was associated with a lower risk of SLE. There was no association between MDM2 T309G polymorphism and SLE.
在系统性红斑狼疮（SLE）患者中，对自身核抗原的免疫耐受丧失和自身反应性 T 和 B 细胞的异常激活导致自身抗体和免疫复合物的产生。在健康个体中，自身反应性淋巴细胞通过凋亡过程被清除；然而，凋亡的破坏可能导致凋亡小体和核碎片的积累。因此，凋亡在自身免疫性疾病的发病机制中起着至关重要的作用。
研究凋亡相关基因 MDM2 中的两个多态性与 SLE 之间的关系。
对 200 例 SLE 患者和 206 例年龄、性别和种族匹配的健康志愿者进行病例对照研究。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和 PCR 方法进行基因分型。
未发现 MDM2 T309G 多态性（rs2279744）与 SLE 之间存在关联。SLE 患者 MDM2 插入/缺失（I/D）多态性（rs3730485）的 ID 基因型显著降低，ID 基因型可能是 SLE 的保护因素。DD 基因型与 SLE 无关。MDM2 T309G 和 I/D 多态性的 TT/ID 和 GG/ID 基因型的联合频率在 SLE 患者中较低，与 SLE 风险较低相关。MDM2 T309G 和 I/D 多态性的 TD 单倍型在 SLE 患者中显著降低，可降低 SLE 风险。
MDM2 I/D 多态性的 ID 基因型与 SLE 风险降低相关。MDM2 T309G 多态性与 SLE 无关。
