Department of Microbiology, Fars Science and Research Branch, Islamic Azad University, Shiraz, Iran AND Department of Microbiology, Shiraz Branch, Islamic Azad University, Shiraz, Iran.
Department of Biochemistry, Kazerun Branch, Islamic Azad University, Kazerun, Iran.
Iran J Allergy Asthma Immunol. 2020 Dec 19;19(6):624-631. doi: 10.18502/ijaai.v19i6.4931.
Acute organ rejection remains a serious clinical challenge. Novel accessible biomarkers of acute rejection could easily enable us to detect the rejection earlier and make more fine-tuned calibration of immunosuppressive or new target treatment possible. Control of gene expression by microRNAs influences many cellular functions, including cellular differentiation, cell proliferation, cell development, and functional regulation of the immune system. Therefore, this study was aimed to investigate if miRNA146a G>C and miRNA196a-2 C>T gene polymorphisms are associated with kidney transplant rejection in Iranian patients. Tissue samples were collected from 100 renal transplant patients between the years 2009 and 2013. The miRNA146a G>C (rs2910164) and miRNA196a-2 C>T (rs11614913) gene polymorphisms were evaluated in kidney transplant patients; using the in-house-polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. In this study, we found that the CC genotype, C and G alleles of the miRNA146a G>C polymorphism was associated with increased risk of transplant rejection in kidney transplant patients (p=0.003, p=0.01 and p=0.01), respectively. The CC genotype, T, and C alleles of the miRNA196a-2 C>T were also significantly more frequent in transplanted patients compared to healthy controls (p=0.02, p=0.05, and p=0.05), respectively. However, significant associations were not found between miRNA196a-2 C>T polymorphisms and kidney transplant rejection. The CC genotype, G, and C allele of the miRNA146a G>C and also, the CC genotype, T and C alleles of the miRNA196a-2 C>T may be genetically susceptible factors for transplant rejection and development of kidney disorders, especially in Iranian patients. Further studies are required to validate these findings in a larger population, as well as in patients with different ethnic origins.
急性器官排斥仍然是一个严重的临床挑战。新型易获取的急性排斥生物标志物可以帮助我们更早地发现排斥反应,并对免疫抑制或新的靶向治疗进行更精细的调整。miRNA 通过控制基因表达来影响许多细胞功能,包括细胞分化、细胞增殖、细胞发育以及免疫系统的功能调节。因此,本研究旨在探讨 miRNA146a G>C 和 miRNA196a-2 C>T 基因多态性是否与伊朗患者的肾移植排斥反应有关。本研究收集了 2009 年至 2013 年间 100 名肾移植患者的组织样本。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测 miRNA146a G>C(rs2910164)和 miRNA196a-2 C>T(rs11614913)基因多态性。在本研究中,我们发现 miRNA146a G>C 多态性的 CC 基因型、C 和 G 等位基因与肾移植患者发生移植排斥的风险增加有关(p=0.003、p=0.01 和 p=0.01)。miRNA196a-2 C>T 的 CC 基因型、T 和 C 等位基因在移植患者中也明显比健康对照组更为常见(p=0.02、p=0.05 和 p=0.05)。然而,miRNA196a-2 C>T 多态性与肾移植排斥之间并未发现显著相关性。miRNA146a G>C 的 CC 基因型、G 和 C 等位基因,以及 miRNA196a-2 C>T 的 CC 基因型、T 和 C 等位基因可能是移植排斥和肾脏疾病发展的遗传易感因素,尤其是在伊朗患者中。需要进一步的研究来验证这些发现,包括在更大的人群中以及不同种族起源的患者中。