CX3CR1基因多态性与维持性血液透析治疗终末期肾病患者微炎症状态的关联

Association of CX3CR1 gene polymorphisms with micro-inflammatory state in patients with end-stage renal disease treated with maintenance haemodialysis

目的探讨CX3CR1基因多态性与维持性血液透析(MHD)治疗终末期肾脏病(ESRD)患者微炎症状态的关联。方法选取2018年5月-2021年5月绍兴市柯桥区中医医院医共体总院行MHD治疗ESRD患者88例(ESRD组)和健康志愿者88名(对照组);分析纳入对象基本资料,采用免疫比浊法检测外周血C-反应蛋白(CRP),酶联吸附法检测外周血白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、CX3CR1和CX3CL1水平,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)检测外周血CX3CR1基因rs3732378、rs3732379多态性并分析基因型、等位基因频率分布情况,分析不同基因型ESRD患者外周血炎性因子和CX3CR1、CX3CL1水平。结果ESRD组肌酐、甘油三酯、CRP、IL-6、TNF-α、CX3CR1和CX3CL1高于对照组(P<0.05),肾小球滤过率低于对照组(P<0.001);ESRD组患者CX3CR1基因rs3732378基因型A/A频率、A等位基因频率和rs3732379基因型C/C频率、C等位基因频率高于对照组(P<0.05),rs3732378基因型G/G频率、G等位基因频率和rs3732379基因型T/T频率、T等位基因频率低于对照组(P<0.05);rs3732378 A/A基因型ESRD患者的CRP、IL-6、TNF-α、CX3CR1和CX3CL1高于A/G+G/G基因型ESRD患者(P<0.05);rs3732379 C/C基因型ESRD患者的CRP、IL-6、TNF-α、CX3CR1和CX3CL1高于C/T+T/T基因型ESRD患者(P<0.05)。结论ESRD患者存在微炎症状态且CX3CR1水平呈升高趋势,CX3CR1基因多态性与ESRD患者的微炎症状态存在密切关系。

OBJECTIVE To investigate the association of CXCR1 gene polymorphisms with microinflammatory status in patients with end-stage renal disease(ESRD)undergoing maintenance hemodialysis(MHD).METHODS A total of 88 patients with ESRD(ESRD group)undergoing MHD and 88 healthy volunteers(control group)in General Hospital of Medical Community,Shaoxing Keqiao Hospital of Traditional Chinese Medicine between May 2018 and May 2021 were selected.The basic information of the included subjects were analyzed.The level of C-reactive protein(CRP)in peripheral blood was detected by immunoturbidimetry.The levels of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),CX3CR1 and CX3CL1 in peripheral blood were detected by enzyme linked immunosorbent assay.The polymorphisms of CX3CR1 gene at rs3732378 and rs3732379 loci were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP),and the distribution of genotypes and allele frequencies were analyzed.The changes in levels of peripheral blood inflammatory factors,CX3CR1 and CX3CL1 in ESRD patients with different genotypes were analyzed.RESULTS The levels of creatinine,triglyceride,CRP,IL-6,TNF-α,CX3CR1 and CX3CL1 of patients in the ESRD group were higher than those in the control group(P<0.05),while glomerular filtration rate was lower than that in the control group(P<0.001).The frequencies of A/A genotype and A allele at CX3CR1 gene's rs3732378 locus,and frequencies of C/C genotype and C allele at rs3732379 locus of patients in the ESRD group were higher than those in the control group(P<0.05),while frequencies of G/G genotype and G allele at rs3732378 locus,and frequencies of T/T genotype and T allele at rs3732379 locus were lower than those in the control group(P<0.05).The levels of CRP,IL-6,TNF-α,CX3CR1 and CX3CL1 in ESRD patients with A/A genotype at rs3732378 locus were higher than those with A/G+G/G genotypes(P<0.05).The levels of CRP,IL-6,TNF-α,CX3CR1 and CX3CL1 in ESRD patients with C/C genotype at rs3732379 locus were higher than those with C/T+T/T genotypes(P<0.05).CONCLUSION The micro-inflammatory state was existed in ESRD patients,and an increased trend in CX3CR1 levels was also observed.The polymorphisms of CX3CR1 gene were closely related to micro-inflammatory state of ESRD patients.