Onel K B, Huo D, Hastings D, Fryer-Biggs J, Crow M K, Onel K
Department of Pediatrics, University of Chicago, Chicago, IL 60637, USA.
Lupus. 2009 Jan;18(1):61-6. doi: 10.1177/0961203308094558.
The p53 tumour suppressor is the central regulator of apoptosis. Previously, the functional TP53 Arg72Pro polymorphism was found to be associated with systemic lupus erythematosus (SLE) in Koreans but not Spaniards. MDM2 is the major negative regulator of p53. An intronic polymorphism in MDM2, the SNP309, attenuates p53 activity and is associated with accelerated tumour development in premenopausal women. Polymorphic variation in MDM2 has never been studied in SLE. The aim of this study is to further assess the contribution of p53-pathway genetic variation to SLE by testing the association of the TP53 Arg72Pro polymorphism and the MDM2 SNP309 with SLE in a well-characterised and ethnically diverse cohort of patients with both childhood- and adult-onset SLE (n = 314). No association was found between the TP53 Arg72Pro polymorphism and SLE in patients of European descent, Asian descent or in African Americans, nor was an association found between the MDM2 SNP309 and SLE in patients of European descent or in African Americans. In addition, there was no correlation between either variant and early-onset disease or nephritis, an index of severe disease. It is concluded that neither the TP53 Arg72Pro polymorphism nor the MDM2 SNP309 contributes significantly to either susceptibility or disease severity in SLE.
p53肿瘤抑制因子是细胞凋亡的核心调节因子。此前，功能性TP53 Arg72Pro多态性被发现与韩国人的系统性红斑狼疮（SLE）相关，但与西班牙人无关。MDM2是p53的主要负调节因子。MDM2中的一个内含子多态性，即SNP309，会减弱p53活性，并与绝经前女性的肿瘤发展加速相关。MDM2的多态性变异在SLE中从未被研究过。本研究的目的是通过检测TP53 Arg72Pro多态性和MDM2 SNP309与一组特征明确且种族多样的儿童期和成人期SLE患者（n = 314）的SLE关联，进一步评估p53信号通路基因变异对SLE的影响。在欧洲裔、亚裔或非裔美国患者中，未发现TP53 Arg72Pro多态性与SLE之间存在关联，在欧洲裔或非裔美国患者中，也未发现MDM2 SNP309与SLE之间存在关联。此外，这两种变异与早发型疾病或肾炎（严重疾病的一个指标）之间均无相关性。结论是，TP53 Arg72Pro多态性和MDM2 SNP309均对SLE的易感性或疾病严重程度没有显著贡献。
