Ismail Nesreen M, Toraih Eman A, Mohammad Mai H S, Alshammari Eida M, Fawzy Manal S
Department of Rheumatology and Rehabilitation, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt.
Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USA.
J Clin Med. 2021 Oct 30;10(21):5095. doi: 10.3390/jcm10215095.
Several microRNAs (miRNAs) are associated with autoimmune disease susceptibility and phenotype, including systemic lupus erythematosus (SLE). We aimed to explore for the first time the role of the miRNA-34a gene (MIR34A) rs2666433A > G variant in SLE risk and severity. A total of 163 adult patients with SLE and matched controls were recruited. Real-Time allelic discrimination PCR was applied for genotyping. Correlation with disease activity and clinic-laboratory data was done. The rs2666433 variant conferred protection against SLE development under heterozygous [A/G vs. G/G; OR = 0.57, 95%CI = 0.34-0.95], homozygous [A/A vs. G/G; OR = 0.52, 95%CI = 0.29-0.94], dominant [A/G + A/A vs. GG; OR = 0.55, 95%CI = 0.35-0.88], and log-additive [OR = 0.71, 95%CI = 0.53-0.95] models. Data stratification by sex revealed a significant association with SLE development in female participants under heterozygous/homozygous models (-interaction = 0.004). There was no clear demarcation between SLE patients carrying different genotypes regarding the disease activity index or patients stratified according to lupus nephritis. Enrichment analysis confirmed the implication of MIR34A in the SLE pathway by targeting several genes related to SLE etiopathology. In conclusion, although the MIR34A rs2666433 variant conferred protection against developing SLE disease in the study population, it showed no association with disease activity. Replication studies in other populations are warranted.
几种微小RNA（miRNA）与自身免疫性疾病易感性和表型相关，包括系统性红斑狼疮（SLE）。我们旨在首次探究miRNA - 34a基因（MIR34A）rs2666433A>G变异在SLE风险和严重程度中的作用。共招募了163例成年SLE患者及匹配的对照组。采用实时等位基因鉴别PCR进行基因分型。分析其与疾病活动度及临床实验室数据的相关性。rs2666433变异在杂合子[A/G vs. G/G；OR = 0.57，95%CI = 0.34 - 0.95]、纯合子[A/A vs. G/G；OR = 0.52，95%CI = 0.29 - 0.94]、显性[A/G + A/A vs. GG；OR = 0.55，95%CI = 0.35 - 0.88]和对数加性[OR = 0.71，95%CI = 0.53 - 0.95]模型下对SLE发病具有保护作用。按性别分层的数据显示，在杂合子/纯合子模型下，女性参与者中该变异与SLE发病存在显著关联（-交互作用 = 0.004）。携带不同基因型的SLE患者在疾病活动指数方面或根据狼疮性肾炎分层的患者之间没有明确界限。富集分析通过靶向几个与SLE病因学相关的基因证实了MIR34A在SLE通路中的作用。总之，尽管在研究人群中MIR34A rs2666433变异对SLE发病具有保护作用，但它与疾病活动度无关。其他人群的重复研究是必要的。
