Renal Division, Peking University First Hospital, Peking University Institute of Nephrology, and Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, People's Republic of China.
Nephrol Dial Transplant. 2011 Aug;26(8):2544-9. doi: 10.1093/ndt/gfq768. Epub 2011 Jan 18.
IgA nephropathy (IgAN) is the leading cause of end-stage renal disease (ESRD) in China considering different compositions of ESRD causes in different ethnicities. A recent genome-wide association study (GWAS) indicated that the MYH9 gene was significantly associated with non-diabetic ESRD in African-Americans and also influenced kidney function in Europeans. Thus, in the present study, we aim to clarify whether MYH9 confers a shared mechanism among different causes of ESRD and to seek possible further insight into our understanding of IgAN by applying GWAS data from ESRD to IgAN.
One thousand one hundred and sixteen Chinese, including 527 patients with renal biopsy-proven IgAN and 589 healthy controls, were enrolled in the present study. Four single neucleotide polymorphisms (SNPs) (rs3752462, rs4821480, rs11089788 and rs2413396) reported to be associated with ESRD with the most significance were genotyped by TaqMan assay or a restriction fragment length polymorphism assay for a further case-control study.
None of the four SNPs was associated with the susceptibility to IgAN or clinical and pathological characters at the time of renal biopsy. However, estimated glomerular filtration rate decline rate was associated with rs11089788 in the dominant model (P = 0.021). Cox regression showed that rs11089788 (hazard ratio, 3.95; 95% confidence interval, 1.23-12.63; P = 2.1 × 10(-2)) was an independent predictive factor for renal survival.
Based on a large Chinese IgAN cohort, we found an association between rs11089788 and prognosis of IgAN, adding to the mounting evidence of MYH9 as an important gene in IgAN to ESRD.
考虑到不同种族的终末期肾病（ESRD）病因构成不同，IgA 肾病（IgAN）是中国导致 ESRD 的主要原因。最近的全基因组关联研究（GWAS）表明，MYH9 基因与非糖尿病性 ESRD 在非裔美国人中显著相关，并且还影响欧洲人的肾功能。因此，在本研究中，我们旨在阐明 MYH9 是否在不同 ESRD 病因之间具有共同的机制，并通过将 ESRD 的 GWAS 数据应用于 IgAN，进一步深入了解 IgAN。
本研究共纳入 1116 名中国人，包括 527 名经肾活检证实的 IgAN 患者和 589 名健康对照者。应用 TaqMan 检测或限制性片段长度多态性检测方法对与 ESRD 最显著相关的 4 个单核苷酸多态性（SNP）（rs3752462、rs4821480、rs11089788 和 rs2413396）进行基因分型，以进一步进行病例对照研究。
这 4 个 SNP 均与 IgAN 的易感性或肾活检时的临床和病理特征无关。然而，在显性模型中，rs11089788 与估算肾小球滤过率下降率相关（P=0.021）。Cox 回归显示，rs11089788（危险比，3.95；95%置信区间，1.23-12.63；P=2.1×10(-2))是肾脏生存的独立预测因素。
基于中国的大型 IgAN 队列，我们发现 rs11089788 与 IgAN 的预后相关，这进一步证明了 MYH9 是 IgAN 发展为 ESRD 的重要基因。
