Kwak Jin Ho, Paek Jin Hyuk, Yu Gyeong Im, Han Seungyeup, Park Woo Yeong, Kim Yaerim, Shin Dong Hoon, Jin Kyubok
Soksiwon Kwak & Lee Clinic, Daegu, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Keimyung University Kidney Institute, Keimyung University School of Medicine, Daegu, Republic of Korea.
Kidney Res Clin Pract. 2022 Jul;41(4):442-451. doi: 10.23876/j.krcp.21.075. Epub 2022 Feb 23.
Chronic kidney disease (CKD) is a common condition leading to renal dysfunction and is closely related to increased cardiovascular and mortality risk. CKD is an important public health issue, and recent genetic studies have verified common CKD susceptibility variants. This research examines the interrelationship between candidate genes polymorphisms of interferon lambda (IFNL) induction, its signaling pathway, and CKD.
Seventy-five patients with advanced CKD and 312 healthy subjects (as controls) participated in this research. A replication set composed of 172 patients with advanced CKD and 365 controls was used for additional analysis. The genotype of single nucleotide polymorphisms (SNPs) was determined by the Axiom Genome-Wide Human Assay and SNaPshot assay.
The SNP of IFNL3 was significantly associated with CKD in the codominant (p = 0.02) and dominant models (p = 0.02). In addition, the SNPs of IFNL2 were significantly associated with CKD in the dominant model (p = 0.03), and the SNP of interferon alpha receptor 2 (IFNAR2) was significantly associated with CKD in the log-additive model (p = 0.03). Concerning rs148543092, in the IFNL3 gene, a significant association was observed after pooling the original and replication sets.
These results indicate that SNPs in the IFNL induction and signal pathway may be associated with CKD risk in the Korean population. Finally, our results also show that the IFNL3 gene variant may be associated with CKD risk.
慢性肾脏病(CKD)是导致肾功能不全的常见病症,与心血管疾病风险增加及死亡率密切相关。CKD是一个重要的公共卫生问题,近期的基因研究已证实常见的CKD易感性变异。本研究探讨了干扰素λ(IFNL)诱导及其信号通路的候选基因多态性与CKD之间的相互关系。
75例晚期CKD患者和312名健康受试者(作为对照)参与了本研究。由172例晚期CKD患者和365名对照组成的重复样本集用于进一步分析。通过Axiom全基因组人类检测法和SNaPshot检测法确定单核苷酸多态性(SNP)的基因型。
IFNL3的SNP在共显性模型(p = 0.02)和显性模型(p = 0.02)中与CKD显著相关。此外,IFNL2的SNP在显性模型中与CKD显著相关(p = 0.03),干扰素α受体2(IFNAR2)的SNP在对数加性模型中与CKD显著相关(p = 0.03)。关于IFNL3基因中的rs148543092,在合并原始样本集和重复样本集后观察到显著关联。
这些结果表明,IFNL诱导和信号通路中的SNP可能与韩国人群的CKD风险相关。最后,我们的结果还表明,IFNL3基因变异可能与CKD风险相关。