IgA Nephropathy Susceptibility Loci and Disease Progression
IgA Nephropathy Susceptibility Loci and Disease Progression
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IgA 肾病易感位点和疾病进展
DOI：
10.2215/cjn.13701217
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发表时间：
2018-09-07
影响因子：
9.8
通讯作者：
Xie, Jingyuan
中科院分区：
文献类型：
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作者：
Shi, Manman;Ouyang, Yan;Xie, Jingyuan
背景和目标 迄今为止，全基因组关联研究已鉴定出至少 20 个 IgA 肾病易感位点。这些位点是否与疾病进展相关尚不清楚。设计、设置、参与者和测量我们招募了 613 名患有 IgA 肾病的成年患者，进行了≥ 12 个月的随访。选择所有 20 个 IgA 肾病易感位点并对其标签单核苷酸多态性 (SNP) 进行基因分型。经过严格的质量控制，16个SNP和517名IgA肾病患者符合后续分析的条件。进展定义为 ESKD 或 eGFR 下降 50%。对 Akaike 信息标准上的所有 SNP 进行逐步 Cox 回归分析，以选择最佳模型。 结果 选择四 SNP 模型 rs11150612 (ITGAM-ITGAX)、rs7634389 (ST6GAL1)、rs2412971 (HORMAD2) 和 rs2856717 (HLA-DQ/DR) 作为最佳预测模型 模型。基于四个 SNP 计算的遗传风险评分与疾病进展前（风险比 [HR]，1.65；95% 置信区间 [95% CI]，1.29 至 2.12）和最近报道的临床模型（HR，1.29；95% CI，1.03 至 1.62）或临床病理模型（HR，1.35；95% CI，1.29 至 2.12）或临床病理模型（HR，1.35；95% CI， 1.03 至 1.77）。与低遗传风险患者相比，中遗传风险患者的进展风险增加2.12倍（95% CI，1.33至3.40），而高遗传风险患者的进展风险增加3.61倍（95% CI，2.00至6.52）。此外，纳入遗传风险评分可能会增加临床模型（c 统计量从 0.83 增加到 0.86）或临床病理模型（c 统计量从 0.82 增加到 0.85）在预测 5 年进展风险时的区分度。 结论 四 SNP 遗传风险评分与 IgA 肾病进展独立相关，可以提高临床和临床病理风险模型的性能。
Background and objectives At least 20 susceptibility loci of IgA nephropathy have been identified by genome-wide association studies to date. Whether these loci were associated with disease progression is unclear.Design, setting, participants, & measurements We enrolled 613 adult patients with IgA nephropathy for a follow-up of >= 12 months. All 20 IgA nephropathy susceptibility loci were selected and their tag single nucleotide polymorphisms (SNPs) were genotyped. After strict quality control, 16 SNPs and 517 patients with IgA nephropathy were eligible for subsequent analysis. Progression was defined as ESKD or 50% decrease in eGFR. A stepwise Cox regression analysis of all SNPs on Akaike information criterion was performed to select the best model.Results A four-SNP model, rs11150612 (ITGAM-ITGAX), rs7634389 (ST6GAL1), rs2412971 (HORMAD2), and rs2856717 (HLA-DQ/DR), was selected as the best predictive model. The genetic risk score calculated on the basis of the four SNPs was independently associated with disease progression before (hazard ratio [HR], 1.65; 95% confidence interval [95% CI], 1.29 to 2.12) and after adjustment by a recently reported clinical model (HR, 1.29; 95% CI, 1.03 to 1.62) or clinical-pathologic model (HR, 1.35; 95% CI, 1.03 to 1.77). Compared with low genetic risk, patients with middle genetic risk had a 2.12-fold (95% CI, 1.33 to 3.40) increase of progression risk, whereas patients with high genetic risk had 3.61-fold (95% CI, 2.00 to 6.52) progression risk increase. In addition, incorporation of genetic risk score could potentially increase discrimination of the clinical model (c-statistic increase from 0.83 to 0.86) or the clinical-pathologic model (c-statistic increase from 0.82 to 0.85) in predicting 5-year progression risk.Conclusions The four-SNP genetic risk score was independently associated with IgA nephropathy progression and could enhance the performance of clinical and clinical-pathologic risk models.