Chua Kek Heng, Lian Lay Hoong, Sim Xiu Jia, Cheah Tien Eang, Lau Tze Pheng
Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Division of Rheumatology, Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Int J Mol Sci. 2015 Apr 29;16(5):9794-803. doi: 10.3390/ijms16059794.
The programmed cell death 1 (PDCD1) gene encodes for the PD-1 (programmed death 1) molecule, which negatively regulates self-reactive T- and B-cells in the maintenance of peripheral tolerance. A previous report had shown the development of lupus-like phenotypes in PD-1-deficient C57BL/6 mice, was suggestive to the role of PDCD1 in predisposing to systemic lupus erythematosus (SLE). Hence, we aimed to investigate the association between PDCD1 and SLE susceptibility in the Malaysian population. A TaqMan-based real-time PCR was employed to screen for PD1.1, PD1.3, PD1.5 and PD1.6 in both SLE and healthy control groups of 200 samples each. The observed frequency for PD1.5C/C genotype was significantly higher in Indian SLE patients and Malay controls (p < 0.01). On the other hand, the PD1.5C/T genotype might predispose the Malays to SLE, but confer a protective effect among the Indians (p < 0.01). The PD1.1, PD1.3 and PD1.6 were, however, not correlated to genetic predisposition of SLE in our Malaysian population. In conclusion, PD1.5 variant was significantly associated to SLE susceptibility in our Malaysian cohort. Our failure in replicating the association between other investigated PDCD1 variants and risk of getting SLE might due to ethnic and geographic variations in the distribution of these genetic variants.
程序性细胞死亡1（PDCD1）基因编码PD-1（程序性死亡1）分子，该分子在维持外周免疫耐受过程中对自身反应性T细胞和B细胞起负向调节作用。先前的一份报告显示，PD-1缺陷的C57BL/6小鼠会出现狼疮样表型，提示PDCD1在系统性红斑狼疮（SLE）易感性中所起的作用。因此，我们旨在研究马来西亚人群中PDCD1与SLE易感性之间的关联。采用基于TaqMan的实时聚合酶链反应对200例SLE患者和200例健康对照样本中的PD1.1、PD1.3、PD1.5和PD1.6进行筛查。观察发现，PD1.5C/C基因型在印度SLE患者和马来族对照中的出现频率显著更高（p<0.01）。另一方面，PD1.5C/T基因型可能使马来人易患SLE，但对印度人有保护作用（p<0.01）。然而，在我们的马来西亚人群中，PD1.1、PD1.3和PD1.6与SLE的遗传易感性无关。总之，在我们的马来西亚队列中，PD1.5变异与SLE易感性显著相关。我们未能重复其他研究的PDCD1变异与患SLE风险之间的关联，可能是由于这些基因变异分布的种族和地理差异。
