A genomic association study revealing subphenotypes of childhood steroid-sensitive nephrotic syndrome in a larger genomic sequencing cohort  

作　　者：Han Chan Fenfen Ni Bo Zhao Huimin Jiang Juanjuan Ding Li Wang Xiaowen Wang Jingjing Cui Shipin Feng Xiaojie Gao Xueying Yang Huan Chi Hao Lee Xuelan Chen Xiaoqin Li Jia Jiao Daoqi Wu Gaofu Zhang Mo Wang Yupeng Cun Xiongzhong Ruan Haiping Yang Qiu Li 

机构地区：[1]Department of Nephrology,Children's Hospital of Chongqing Medical University,National Clinical Research Center for Child Health and Disorders,Ministry of Education Key Laboratory of Child Development and Disorders,Chongqing Key Laboratory of Pediatrics,Chongqing 400014,China [2]Department of Nephrology,Shenzhen Children's Hospital,Shenzhen,Guangdong 518034,China [3]Department of Nephrology,Kunming Children's Hospital,Kunming Medical University,Kunming,Yunnan 650228,China [4]Department of Nephrology,Wuhan Children's Hospital,Tongji Medical College of Huazhong University of Science and Technology,Wuhan,Hubei 430015,China [5]Department of Nephrology,Chengdu Women and Children Central Hospital,Chengdu,Sichuan 610073,China [6]Pediatric Research Institute,Ministry of Education Key Laboratory of Child Development and Disorders,National Clinical Research Center for Child Health and Disorders,China International Science and Technology Cooperation Base of Child Development and Critical Disorders,Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders,Children's Hospital of Chongqing Medical University,Chongqing 400014,China [7]Department of Nephrology,John Moorhead Research Laboratory,University College London Medical School,Royal Free Campus,University College London,London NW32PF,United Kingdom

出　　处：《Genes & Diseases》2024年第4期400-410,共11页基因与疾病（英文）

基　　金：funded by the China National Natural Science Foundation(No.81970618,82170720,82200788);China National Clinical Research Centre Foundation(No.NCRC-2019-GP-02);Science and Technology Research Project of Chongqing Education Commission of China(No.KJZDM201900401);Chongqing Science and Health Joint Medical Research Project(China)(No.2023GGXM001);National Key R&D Program of China(No.2022YFC2705101).

摘　　要：Dissecting the genetic components that contribute to the two main subphenotypes of steroid-sensitive nephrotic syndrome(SSNS)using genome-wide association studies(GWAS)strategy is important for understanding the disease.We conducted a multicenter cohort study(360 patients and 1835 controls)combined with a GWAS strategy to identify susceptibility var-iants associated with the following two subphenotypes of ssNS:steroid-sensitive nephrotic syn-drome without relapse(SSNswR,181 patients)and steroid-dependent/frequent relapse nephrotic syndrome(SDNS/FRNS,179 patients).The distribution of two single-nucleotide poly-morphisms(SNPs)in ANKRD36 and ALPG was significant between SSNSWR and healthy controls,and that of two SNPs in GAD1 and HLA-DQA1 was significant between SDNS/FRNS and healthy controls.Interestingly,rs1047989 in HLA-DQA1 was a candidate locus for SDNS/FRNS but not for SSNSWR.No significant SNPs were observed between SSNSWR and SDNS/FRNS.Meanwhile,chromosome 2:171713702 in GAD1 was associated with a greater steroid dose(>0.75 mg/kg/d)upon relapse to first remission in patients with SDNS/FRNS(odds ratio=3.14;95%confidence interval,0.97-9.87;P=0.034).rs117014418 in APOL4 was significantly associated with a decrease in eGFR of greater than 20%compared with the baseline in SDNS/FRNS patients(P=0.0001).Protein-protein intersection network construction suggested that HLA-DQA1 and HLA-DQB1 function together through GSDMA.Thus,SSNSWR belongs to non-HLA region-dependent nephropathy,and the HLA-DQA/DQB region is likely strongly associated with dis-ease relapse,especially in SDNS/FRNS.The study provides a novel approach for the GWAS strategy of SsNS and contributes to our understanding of the pathological mechanisms of SSNSWRandSDNS/FRNS.

关 键 词：Frequentrelapse Genome-wide association study Human leukocyte antigen region Steroid-sensitive nephrotic syndrome 

分 类 号：R692[医药卫生—泌尿科学]