Zhou Qiongxiu, Weng Qinjie, Zhang Xiaoyan, Liu Yunzi, Tong Jun, Hao Xu, Shi Hao, Shen Pingyan, Ren Hong, Xie Jingyuan, Chen Nan
Department of Nephrology, Institute of Nephrology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Nephrology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Med (Lausanne). 2022 Jul 22;9:937122. doi: 10.3389/fmed.2022.937122. eCollection 2022.
is the coding gene of podocin. This study aims to investigate the association between p.R229Q (rs61747728), the most frequently reported missense variant of , and focal segmental glomerular sclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) based on typing the variant in a Chinese FSGS/SRNS cohort and conducting a meta-analysis.
We recruited patients with FSGS or SRNS and healthy individuals. To conduct a meta-analysis, all studies on p.R229Q and FSGS/SRNS were searched from public databases.
In total, we enrolled 204 patients with FSGS, 61 patients with SRNS [46 with FSGS, 9 with minimal change disease (MCD), and six patients with IgA nephropathy (IgAN)], and 100 healthy controls. Unexpectedly, p.R229Q was absent in the patients from our cohort. By meta-analysis of 21 studies including 2,489 patients with FSGS/SRNS and 6,004 healthy controls, we confirmed that the A allele of p.R229Q was significantly associated with increased risk of FSGS/SRNS (allelic OR = 1.9, 95% CI = 1.44-2.52, < 0.001). However, the subgroup analysis showed that the association between p.R229Q and FSGS/SRNS was true only in Caucasians (allelic OR = 2.14, 95%CI = 1.54-2.98, < 0.001) and in early-onset patients (allelic OR: 2.13, 95% CI = 1.21-3.76, = 0.009).
p.R229Q may play an important role in enhancing the susceptibility of FSGS/SRNS, especially in ethnicity of Caucasian and age of early-onset patients.
是足突蛋白的编码基因。本研究旨在通过对中国FSGS/SRNS队列中的该变异进行分型，并进行荟萃分析，探讨p.R229Q（rs61747728）（最常报道的错义变异）与局灶节段性肾小球硬化（FSGS）或激素抵抗型肾病综合征（SRNS）之间的关联。
我们招募了FSGS或SRNS患者以及健康个体。为进行荟萃分析，从公共数据库中检索了所有关于p.R229Q与FSGS/SRNS的研究。
我们共纳入了204例FSGS患者、61例SRNS患者[46例FSGS、9例微小病变肾病（MCD）和6例IgA肾病（IgAN）]以及100例健康对照。出乎意料的是，我们队列中的患者不存在p.R229Q。通过对21项研究（包括2489例FSGS/SRNS患者和6004例健康对照）的荟萃分析，我们证实p.R229Q的A等位基因与FSGS/SRNS风险增加显著相关（等位基因比值比=1.9，95%置信区间=1.44 - 2.52，P<0.001）。然而，亚组分析表明，p.R229Q与FSGS/SRNS之间的关联仅在白种人（等位基因比值比=2.14，95%置信区间=1.54 - 2.98，P<0.001）和早发患者（等位基因比值比：2.13，95%置信区间=1.21 - 3.76，P = 0.009）中成立。
p.R229Q可能在增强FSGS/SRNS易感性方面起重要作用，尤其是在白种人种族和早发患者年龄组中。
