Zhang Junlong, Meng Yanming, Wu Hengxu, Wu Yongkang, Yang Bin, Wang Lanlan
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Medicine (Baltimore). 2018 Jul;97(27):e11451. doi: 10.1097/MD.0000000000011451.
Increasing evidence supports the involvement of a catalytic subunit (PP2Ac) of protein phosphatase 2A (PP2A) in the mechanisms of systemic lupus erythematosus (SLE). This study was conducted to explore the association single nucleotide polymorphisms (SNPs) of PPP2CA with SLE susceptibility, serum cytokines levels, and clinical features in a Chinese Han population. A case-control association study was carried out in 1509 Chinese Han subjects (730 SLE patients and 779 healthy individuals). Genotyping for genetic variants of PPP2CA (rs10491322 and rs7704116) was performed using a polymerase chain reaction-high resolution melting (PCR-HRM) assay. In the cohort of SLE patients, we observed that rs10491322 and rs7704116 were positively increased SLE susceptibility (OR = 1.61, 95% CI = 1.13-2.31, P = .009; OR = 1.59, 95% CI = 1.17-2.15, P = .003, respectively). Interestingly, the AG genotype of rs10491322 carriers presented higher IL-6 (P < .001) and IL-17 (P < .001) than those with AA genotype carriers. Specifically, carriage of the rs10491322 G* allele led to a higher prevalence of arthritis in SLE patients (P = .01). This study demonstrated an association of PPP2CA (rs10491322 and rs7704116) with SLE susceptibility in a Chinese Han population. Furthermore, the minor allele of PPP2CA rs10491322 as a risk factor was correlated with immunologic disorders for SLE.
越来越多的证据支持蛋白磷酸酶2A(PP2A)的催化亚基(PP2Ac)参与系统性红斑狼疮(SLE)的发病机制。本研究旨在探讨蛋白磷酸酶2A催化亚基基因(PPP2CA)单核苷酸多态性(SNP)与中国汉族人群SLE易感性、血清细胞因子水平及临床特征的相关性。对1509名中国汉族受试者(730例SLE患者和779名健康个体)进行了病例对照关联研究。采用聚合酶链反应-高分辨率熔解曲线分析(PCR-HRM)对PPP2CA基因变异(rs10491322和rs7704116)进行基因分型。在SLE患者队列中,我们观察到rs10491322和rs7704116均使SLE易感性显著增加(OR分别为1.61,95%CI为1.13-2.31,P=0.009;OR为1.59,95%CI为1.17-2.15,P=0.003)。有趣的是,rs10491322携带者的AG基因型比AA基因型携带者表现出更高的IL-6(P<0.001)和IL-17(P<0.001)水平。具体而言,携带rs10491322 G*等位基因的SLE患者关节炎患病率更高(P=0.01)。本研究证明了PPP2CA(rs10491322和rs7704116)与中国汉族人群SLE易感性相关。此外,PPP2CA rs10491322的次要等位基因作为危险因素与SLE的免疫紊乱相关。