rs6677604单核苷酸多态性与IgA肾病患者系膜C3沉积和预后的差异比较
Comparisons of mesangial C3 deposition and prognosis in IgA nephropathy patients with different rs6677604 single nucleotide polymorphisms
摘要目的:比较rs6677604单核苷酸多态性(SNP)与免疫球蛋白A(IgA)肾病患者系膜C3沉积和预后的差异。方法:采用回顾性巢式病例对照分析。收集台州市中心医院2018年7月至2021年7月收治的IgA肾病患者380例的临床资料,患者均检测rs6677604 SNP,从中选取AG基因型36例,GG基因型72例。比较两种基因型临床资料(IgA、C4和C3免疫沉积物评分,经皮肾活检术,间质纤维化/肾小管萎缩,系膜C3沉积)、组织和循环补体水平、CFHR基因拷贝数;定期随访2年,分析不同rs6677604 SNP患者的预后。结果:rs6677604-AG基因型患者IgA、C4、C3免疫沉积物得分分别为(1.34±0.50)分、(1.47±0.31)分、(2.65±0.36)分,均低于rs6677604-GG基因型患者的(1.77±0.73)分、(2.17±0.33)分、(3.00±0.48)分( t=-3.17、-10.59、-3.86,均 P < 0.05),系膜C3沉积强度以2+居多,循环C3、C4和补体因子H(CFH)均高于rs6677604-GG基因型患者( t=7.90、9.87、2.27,均 P < 0.05),循环IgA和Gd-IgA1水平均低于rs6677604-GG基因型患者( t=-2.98、-2.08,均 P < 0.05)。rs6677604-AG基因型患者CFHR3基因均为1拷贝,CFHR1基因33例(91.67%)1拷贝,3例(8.33%)2拷贝;rs6677604-GG基因型患者CFHR3和CFHR1基因均为2拷贝。rs6677604-AG和rs6677604-GG基因型患者2年内复合终点差异无统计学意义(χ 2=0.19, P=0.656)。 结论:rs6677604 SNP与IgA肾病患者循环CFH水平和系膜C3沉积具有相关性,可能对IgA肾病中的补体激活具有调节作用。
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abstractsObjective:To correlate rs6677604 single nucleotide polymorphism (SNP) with mesangial C3 deposition and prognosis among patients with IgA nephropathy.Methods:A retrospective nested case-control study was conducted among 380 patients with IgA nephropathy who received treatment at Taizhou Central Hospital from July 2018 to July 2021. All patients were tested for rs6677604 SNP. Among them, 36 AG genotypes and 72 GG genotypes were selected. The clinical data (IgA, C4, C3 deposit scores, percutaneous kidney biopsy, interstitial fibrosis/glomerular atrophy, mesangial C3 deposition), tissue and circulating complement levels, and CFHR gene copy numbers were compared between two genotypes. Regular follow-ups were conducted for 2 years to analyze the prognosis of patients with different rs6677604 genotypes. Results:Patients with the rs6677604-AG genotype had scores of (1.34 ± 0.50) points for IgA, (1.47 ± 0.31) points for C4 deposit, and (2.65 ± 0.36) points for C3 deposit, all of which were significantly lower than those in patients with rs6677604-GG genotype [(1.77 ± 0.73) points, (2.17 ± 0.33) points, (3.00 ± 0.48) points, t = -3.17, -10.59, -3.86, all P < 0.05]. The deposition intensity of mesangial C3 was predominantly 2+. Circulating levels of C3, C4, and complement factor H were significantly higher in patients with rs6677604-AG genotype compared with patients with rs6677604-GG genotype ( t = 7.90, 9.87, 2.27, all P < 0.05). Circulating levels of IgA and Gd-IgA1 were significantly lower in patients with rs6677604-AG genotype compared with those with rs6677604-GG genotype ( t = -2.98, -2.08, both P < 0.05). All patients with rs6677604-AG genotype had 1 copy of the CFHR3 gene, with 33 cases (91.67%) having 1 copy and 3 cases (8.33%) having 2 copies of the CFHR1 gene. Both CFHR3 and CFHR1 genes in patients with rs6677604-GG genotype were 2 copies. There was no statistically significant difference in composite endpoint between patients with rs6677604-AG and rs6677604-GG genotypes over the 2-year period (χ 2 = 0.19, P = 0.656). Conclusion:RS6677604 SNP is correlated with circulating complement factor H levels and mesangial C3 deposition in patients with IgA nephropathy, and may have a regulatory effect on complement activation in IgA nephropathy.
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