Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
NHC Key Laboratory of Clinical Nephrology (Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of Nephrology, Guangzhou, China.
Kidney Blood Press Res. 2023;48(1):436-444. doi: 10.1159/000530262. Epub 2023 Apr 14.
A previous genome-wide association study has identified CARD9 (caspase recruitment domain family member 9) as a susceptibility gene for immunoglobulin A nephropathy (IgAN), which encodes an adapter protein and is related to mucosal immunity. This study aimed to investigate the association of CARD9 variants with the clinicopathological phenotypes and prognosis of IgAN.
Eight single nucleotide polymorphisms within CARD9 were genotyped using Sequenom MassARRAY iPLEX for 986 IgAN patients in this study. Logistic and linear regression analyses adjusted for age and gender were performed to evaluate the effects of CARD9 gene polymorphisms on clinicopathological phenotypes. The Kaplan-Meier method and Cox proportional hazard models were applied to analyze the associations between genetic variants and renal survival.
The T allele of rs10747047 was strongly associated with higher levels of serum creatinine (p = 0.005) and lower levels of estimated glomerular filtration rate (p = 0.005). The rs10870149-G and rs10870077-C alleles were associated with elevated 24-h urine protein excretion (p = 0.041 and 0.022, respectively) and more serious segmental glomerulosclerosis lesions (p = 0.005 and 0.041, respectively) in IgAN patients. Carriers with the T allele of rs10781533 and the C allele of rs3812552 also presented with severe segmental glomerulosclerosis lesions (p = 0.001 and 0.010, respectively). Additionally, rs10747047-C and rs10870077-C alleles were independently related to the poor prognosis of IgAN patients after adjustments for covariates (TT vs. CC hazard ratio [HR] = 0.138, 95% confidence interval [95% CI] = 0.022-0.871, p = 0.035; GG vs. CC HR = 0.321, 95% CI = 0.123, 0.836, p = 0.020, respectively).
CARD9 variants are associated with disease severity and rapid disease progression for IgAN in a Chinese Han population.
先前的全基因组关联研究已经确定 CARD9（半胱氨酸天冬氨酸蛋白酶募集域家族成员 9）是免疫球蛋白 A 肾病（IgAN）的易感基因，它编码一种衔接蛋白，与黏膜免疫有关。本研究旨在探讨 CARD9 变异与 IgAN 的临床病理表型和预后的关系。
本研究对 986 例 IgAN 患者的 CARD9 内的 8 个单核苷酸多态性进行了 Sequenom MassARRAY iPLEX 基因分型。对年龄和性别进行了 logistic 和线性回归分析，以评估 CARD9 基因多态性对临床病理表型的影响。应用 Kaplan-Meier 法和 Cox 比例风险模型分析遗传变异与肾脏存活率之间的关系。
rs10747047 的 T 等位基因与血清肌酐水平升高（p = 0.005）和估算肾小球滤过率水平降低（p = 0.005）显著相关。rs10870149-G 和 rs10870077-C 等位基因与 24 小时尿蛋白排泄量增加（p = 0.041 和 0.022）和更严重的节段性肾小球硬化病变（p = 0.005 和 0.041）相关。rs10781533 的 T 等位基因和 rs3812552 的 C 等位基因携带者也表现出严重的节段性肾小球硬化病变（p = 0.001 和 0.010）。此外，在调整协变量后，rs10747047-C 和 rs10870077-C 等位基因与 IgAN 患者的不良预后独立相关（TT 与 CC 风险比[HR] = 0.138，95%置信区间[95%CI] = 0.022-0.871，p = 0.035；GG 与 CC HR = 0.321，95%CI = 0.123-0.836，p = 0.020）。
在中国汉族人群中，CARD9 变异与 IgAN 的疾病严重程度和快速疾病进展有关。
