Department of Biotechnology, LCWU, Lahore, Pakistan.
Department of Clinical and Biomedical Science, University of Exeter Medical School, Exeter, UK.
Mol Biol Rep. 2024 Aug 31;51(1):947. doi: 10.1007/s11033-024-09873-z.
End stage renal disease (ESRD) occurs when the kidneys are unable to filter the waste products and excessive fluids from the blood that results into the accumulation of toxins and fluid in the body. Tacrolimus is commonly used immunosuppressant while sirolimus and cyclosporin are rarely used drugs to stop solid organ transplant rejection. The host's immunological response following transplantation produces interleukin-10 (IL-10), which influences the varied CYP3A-dependent drug disposition of tacrolimus. The aim of this study was to determine the genetic polymorphisms of IL-10 (rs1800871, rs1800872 and rs1800896) gene associated with tacrolimus metabolism in kidney transplant patients from Lahore Punjab, Pakistan.
The study collected blood samples of 103 healthy individuals and 137 kidney transplant patients as control and treatment groups, respectively. We employed Tetra ARMS PCR for the genotype analysis of extracted DNA. The alleles were called on 2% agarose gel. Moreover, the study utilized SPSS software to analyze statistical significance of polymorphism.
It was found that genotypic frequencies of IL-10 (rs1800871), IL-10 (rs1800872), and IL-10 (rs1800896) were (TT: 66.4%; TC: 31.4%; CC: 2.2%), (AA: 27.7%; AC: 54%; CC: 18.2%), (AA: 64.2%; GA: 17.5%; GG: 18.3%), respectively among kidney transplant patients. All parameters show significant association at different points after transplantation. Genetic analysis showed that TC and CC genotypes in rs1800871 (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 3.370 (0.642-17.672), P = 0.150), AC and CC genotypes in rs1800872 (OR (95%CI) = 1.294 (0.695-2.410), P = 0.415; OR (95%CI) = 1.453 (0.671-3.147), P = 0.342), GA and GG genotypes in rs1800896 (OR (95%CI) = 42.952 (17.566-105.021), P = 0.001; OR (95%CI) = 7.040 (2.563-19.333), P = 0.342) was associated with risk of renal rejection in kidney transplant patients. Besides, genetic models showed that TT in rs1800871, AA genotypes in rs1800872 and rs1800892 were associated with risk of renal rejection under dominant model when compared to controls (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 1.335 (0.735-9.290), P < 0.341; OR (95%CI) = 24.629 (10.599-57.230), P < 0.001), respectively.
From the results, it is concluded that genetic polymorphism of IL-10 (rs1800871, rs1800872 and rs1800896) has a highly significant association with risk of renal rejection in Pakistani kidney transplant patients.
当肾脏无法过滤血液中的废物和过多的液体，导致毒素和液体在体内积聚时，就会发生终末期肾脏疾病 (ESRD)。他克莫司通常被用作免疫抑制剂，而西罗莫司和环孢素则很少被用作阻止实体器官移植排斥反应的药物。移植后宿主的免疫反应会产生白细胞介素-10 (IL-10)，这会影响他克莫司的各种 CYP3A 依赖性药物处置。本研究的目的是确定白细胞介素-10 (rs1800871、rs1800872 和 rs1800896) 基因多态性与巴基斯坦拉合尔旁遮普省肾移植患者他克莫司代谢的关系。
该研究采集了 103 名健康个体和 137 名肾移植患者的血液样本，分别作为对照组和治疗组。我们采用 Tetra ARMS PCR 对提取的 DNA 进行基因型分析。等位基因在 2%琼脂糖凝胶上进行呼叫。此外，该研究还利用 SPSS 软件分析了多态性的统计学意义。
研究发现，肾移植患者白细胞介素-10 (rs1800871)、白细胞介素-10 (rs1800872) 和白细胞介素-10 (rs1800896) 的基因型频率分别为 (TT: 66.4%; TC: 31.4%; CC: 2.2%)、(AA: 27.7%; AC: 54%; CC: 18.2%)、(AA: 64.2%; GA: 17.5%; GG: 18.3%)。所有参数在移植后不同时间均显示出显著关联。遗传分析显示，rs1800871 中的 TC 和 CC 基因型 (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 3.370 (0.642-17.672), P = 0.150)、rs1800872 中的 AC 和 CC 基因型 (OR (95%CI) = 1.294 (0.695-2.410), P = 0.415; OR (95%CI) = 1.453 (0.671-3.147), P = 0.342)、rs1800896 中的 GA 和 GG 基因型 (OR (95%CI) = 42.952 (17.566-105.021), P = 0.001; OR (95%CI) = 7.040 (2.563-19.333), P = 0.342) 与肾移植患者的肾排斥风险相关。此外，遗传模型显示，与对照组相比，rs1800871 中的 TT、rs1800872 和 rs1800892 中的 AA 基因型在显性模型下与肾排斥风险相关 (OR (95%CI) = 5.721 (3.231-10.131), P < 0.001; OR (95%CI) = 1.335 (0.735-9.290), P < 0.341; OR (95%CI) = 24.629 (10.599-57.230), P < 0.001)。
从结果可以得出结论，白细胞介素-10 (rs1800871、rs1800872 和 rs1800896) 的遗传多态性与巴基斯坦肾移植患者的肾排斥风险高度相关。
