肾素-血管紧张素系统基因多态性与Ig A肾病肾损伤的关系  

The Relationship between Renin-angiotensin System Gene Polymorphisms and Renal Injury in IgA Nephropathy

作　　者：李晨雨绮 王旭[1] 杨悦[1] 姜世敏 邹古明[1] 高红梅[1] 李文歌[1] 张铮[1] LI Chen-yu-qi;WANG Xu;YANG Yue;JIANG Shi-min;ZOU Gu-ming;GAO Hong-mei;LI Wen-ge;ZHANG Zheng(China-Japan Friendship Hospital,Nephrology,Beijing,100029,China)

机构地区：[1]中日友好医院肾病科,北京100029

出　　处：《现代生物医学进展》2025年第3期411-418,450,共9页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(82304363)。

摘　　要：目的:探讨IgA肾病(IgA nephropathy,IgAN)患者中肾素-血管紧张素系统的3个主要基因多态性位点,单核苷酸多态性与IgAN肾脏损伤的关系。方法:2018年1月-2022年9月在中日友好医院肾病科行肾穿刺活检确诊为IgAN的患者317例。从IgAN患者外周血或肾组织中提取DNA,检测血管紧张素原(AGT)编码基因的M235T位点、血管紧张素1型受体(AT1R)编码基因的A1166C位点、血管紧张素2型受体(AT2R)编码基因的A1675G位点的基因型,分析不同基因型与Ig AN临床表现及预后的相关性。结果:A1166C位点的AA基因型患者24 h尿蛋白定量(P=0.019)、血肌酐(P=0.034)较AC基因型显著高,AA基因型患者eGFR明显低于AC基因型患者(P=0.026)。M235T和A1675G各基因型患者临床表现上未见明显差异。Kaplan-Meier单因素分析显示,A1166C的AA基因型患者肾脏生存率显著低于AC基因型(P=0.039),A1675G位点的AA基因型IgAN患者血肌酐(P=0.025)显著高于AG基因型,M235T各基因型患者间无显著性差异。结论:在编码AT1R基因的A1166C位点中,携带A等位基因的IgAN患者临床表现重、肾功能损害进展快,因此,为A1166C的AA基因型患者制定个体化治疗方案对改善预后尤为重要。未来对A1166C位点所编码蛋白的研究可能为Ig AN的治疗提供新的靶向药物研发方向。Objective:To investigate the association between single nucleotide polymorphisms(SNPs)in three key genes of the renin-angiotensin system and renal injury in patients with IgA nephropathy(IgAN).Methods:A total of 317 patients diagnosed with Ig AN by renal biopsy at the Department of Nephrology,China-Japan Friendship Hospital,from January 2018 to September 2022 were included.DNA was extracted from peripheral blood or renal tissue of these patients.The three SNPs studied are M235T in the angiotensinogen(AGT)gene,A1166C in the angiotensin I receptor(AT1R)gene,and A1675G in the angiotensin Ⅱ receptor(AT2R)gene.The genotypes of AGT gene M235T,AT1R gene A1166C,and AT2R gene A1675G were analyzed to explore their association with clinical manifestations and prognosis of IgAN.Results:Patients with the AA genotype of A1166C had significantly higher 24-hour urinary protein quantification(P=0.019)and serum creatinine(P=0.034),and significantly lower eGFR(P=0.026)compared to those with the AC genotype.The serum creatinine level in IgAN patients with the AA genotype at the A1675G site was significantly higher than that in patients with the AG genotype(P=0.025).No significant clinical differences were observed between different genotypes of M235T.Kaplan-Meier univariate analysis showed that patients with the AA genotype of A1166C had a significantly lower renal survival rate compared to those with the AC genotype(P=0.039),with no significant differences observed between genotypes for M235T and A1675G.Conclusion:The presence of the A allele at the A1166C locus in the AT1R gene is associated with faster progression of renal function impairment in IgA nephropathy patients.Therefore,developing individualized treatment plans for patients with the AA genotype of A1166C is crucial for improving prognosis.Future research on the protein encoded by the A1166C locus may provide new targeted therapeutic options for Ig AN.

关 键 词：IgA肾病 基因多态性 血管紧张素受体 血管紧张素原 

分 类 号：R3[医药卫生—基础医学] R394.3R692.6