Department of Internal Medicine, Hallym University Hangang Sacred Heart Hospital, Seoul, Korea.
Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul, Korea.
PLoS One. 2018 Mar 20;13(3):e0194044. doi: 10.1371/journal.pone.0194044. eCollection 2018.
Chronic kidney disease (CKD) is an important social health problem characterized by a decrease in the kidney glomerular filtration rate (GFR). In this study, we analyzed genome-wide association studies for kidney disease-related traits using data from a Korean adult health screening cohort comprising 7,064 participants. Kidney disease-related traits analyzed include blood urea nitrogen (BUN), serum creatinine, estimated GFR, and uric acid levels. We detected two genetic loci (SLC14A2 and an intergenic region) and 8 single nucleotide polymorphisms (SNPs) associated with BUN, 3 genetic loci (BCAS3, C17orf82, ALDH2) and 6 SNPs associated with serum creatinine, 3 genetic loci (BCAS3, C17orf82/TBX2, LRP2) and 7 SNPs associated with GFR, and 14 genetic loci (3 in ABCG2/PKD2, 2 in SLC2A9, 3 in intergenic regions on chromosome 4; OTUB1, NRXN2/SLC22A12, CDC42BPG, RPS6KA4, SLC22A9, and MAP4K2 on chromosome 11) and 84 SNPs associated with uric acid levels. By comparing significant genetic loci associated with serum creatinine levels and GFR, rs9895661 in BCAS3 and rs757608 in C17orf82 were simultaneously associated with both traits. The SNPs rs11710227 in intergenic regions on chromosome 3 showing significant association with BUN is newly discovered. Genetic variations of multiple gene loci are associated with kidney disease-related traits, and differences in associations between kidney disease-related traits and genetic variation are dependent on the population. The meanings of the mutations identified in this study will need to be reaffirmed in other population groups in the future.
慢性肾脏病（CKD）是一个重要的社会健康问题，其特征是肾小球滤过率（GFR）下降。本研究利用韩国成人健康筛查队列（包含 7064 名参与者）的数据，对与肾脏疾病相关的特征进行了全基因组关联研究。分析的与肾脏疾病相关的特征包括血尿素氮（BUN）、血清肌酐、估计肾小球滤过率（eGFR）和尿酸水平。我们检测到与 BUN 相关的两个遗传位点（SLC14A2 和一个基因间区域）和 8 个单核苷酸多态性（SNP），与血清肌酐相关的 3 个遗传位点（BCAS3、C17orf82、ALDH2）和 6 个 SNP，与 GFR 相关的 3 个遗传位点（BCAS3、C17orf82/TBX2、LRP2）和 7 个 SNP，与尿酸水平相关的 14 个遗传位点（ABCG2/PKD2 中的 3 个，SLC2A9 中的 2 个，染色体 4 上基因间区域中的 3 个；OTUB1、NRXN2/SLC22A12、CDC42BPG、RPS6KA4、SLC22A9 和 MAP4K2）和 84 个 SNP。通过比较与血清肌酐水平和 GFR 相关的显著遗传位点，BCAS3 中的 rs9895661 和 C17orf82 中的 rs757608 同时与这两个特征相关。染色体 3 上基因间区域中与 BUN 显著相关的 rs11710227 是新发现的。多个基因座的遗传变异与肾脏疾病相关特征有关，肾脏疾病相关特征与遗传变异之间的关联差异取决于人群。本研究中鉴定的突变的意义需要在未来的其他人群中重新确认。
