Luo Xiaoning, Du Juanhua, Zhao Jinjun, Fan Meida, Luo Xin, Zhao Peijin, Zheng Ping, Mo Liqian, Li Yilei
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Lupus. 2024 Oct;33(12):1328-1335. doi: 10.1177/09612033241281783. Epub 2024 Sep 17.
This study aims to explore possible susceptibility genes and clinical features for systemic lupus erythematosus (SLE) patients in a Chinese population.
Expanding on the results of a prior single-center observational study involving 60 systemic lupus erythematosus patients, a subsequent single-center prospective observational study was conducted on SLE patients undergoing treatment at Nanfang Hospital Affiliated to Southern Medical University from 2021 to 2023. The identification process for drug-related target genes entailed an extensive search across PharmGKB (https://www.pharmgkb.org/), the Clinical Pharmacogenetics Implementation Consortium (CPIC),and PubMed literature databases, to pinpoint common drugs and target single nucleotide polymorphisms(SNPs)for SLE. Blood samples were individually collected and genotyped using MassARRAY® high-throughput nucleic acid mass spectrometry. Genotype frequency differences were assessed through Chi-square tests against both the larger East Asian population as well as kidney transplant recipients. Data collection relied on electronic medical records, encompassing demographic details(age, gender),medication regimens(hormones, NSAIDs, hydroxychloroquine, DMARDs, biologic agents, stomach medications, calcitriol, etc.),laboratory indicators(RF, Anti-CCP antibody, ESR, CRP, anti-ANA antibodies, dsDNA antibodies, anti-SM antibodies, S m. RNP antibodies, A LT, ALB, CR, UA, WBC, PLT, HGB, Ca, K, Glu, CHOL, TG, LDL-C, HDL-C) and lupus activity scores(SLEDAI-2K). Possible disease susceptibility genes were categorized, and SPSS26 software facilitated statistical analyses.
The research encompassed a total of 137 SLE patients along with 50 SNPs. After conducting statistical analyses, it emerged that there existed significant disparities in gene (rs1065852) distribution when compared against allele mutation rates within both East Asian populations ( < .05) and kidney transplant patients( < .05). Wild-type gene (GG) constituted 14% of cases while mutant gene (GA + AA) constituted 86%. Allele mutation rate (A63.6%) was significantly higher among SLE patients (RR = 0.802; = .0355). Furthermore, the variant rs1065852 genotype (GA + AA) demonstrated significant associations with lower CRP levels, higher HGB levels, and higher HDL-C levels ( < 0 0.05).
The metabolic enzyme CYP2D6 may be used as susceptibility gene for predicting systemic lupus erythematosus and are correlated with CRP and other indicators.
本研究旨在探索中国人群中系统性红斑狼疮（SLE）患者可能的易感基因和临床特征。
在先前一项涉及60例系统性红斑狼疮患者的单中心观察性研究结果基础上，于2021年至2023年对在南方医科大学南方医院接受治疗的SLE患者进行了一项单中心前瞻性观察性研究。药物相关靶基因的鉴定过程需要在PharmGKB（https://www.pharmgkb.org/）、临床药物基因组学实施联盟（CPIC）和PubMed文献数据库中进行广泛搜索，以确定SLE的常用药物和靶单核苷酸多态性（SNP）。分别采集血样并使用MassARRAY®高通量核酸质谱进行基因分型。通过卡方检验评估与更大的东亚人群以及肾移植受者的基因型频率差异。数据收集依赖电子病历，包括人口统计学细节（年龄、性别）、用药方案（激素、非甾体抗炎药、羟氯喹、抗风湿药物、生物制剂、胃药、骨化三醇等）、实验室指标（类风湿因子、抗环瓜氨酸肽抗体、血沉、C反应蛋白、抗核抗体、双链DNA抗体、抗Sm抗体、Sm/RNP抗体、谷丙转氨酶、白蛋白、肌酐、尿酸、白细胞、血小板、血红蛋白、钙、钾、葡萄糖、胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇）和狼疮活动评分（SLEDAI - 2K）。对可能的疾病易感基因进行分类，并使用SPSS26软件进行统计分析。
该研究共纳入137例SLE患者和50个SNP。经过统计分析，发现与东亚人群（P <.05）和肾移植患者（P <.05）的等位基因突变率相比，基因（rs1065852）分布存在显著差异。野生型基因（GG）占病例的14%，而突变基因（GA + AA）占86%。SLE患者的等位基因突变率（A 63.6%）显著更高（RR = 0.802；P =.0355）。此外，rs1065852变异基因型（GA + AA）与较低的C反应蛋白水平、较高的血红蛋白水平和较高的高密度脂蛋白胆固醇水平显著相关（P < 0.05）。
代谢酶CYP2D6可作为预测系统性红斑狼疮的易感基因，并与C反应蛋白等指标相关。
