Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Nephrology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Nephron. 2020;144(4):204-212. doi: 10.1159/000505296. Epub 2020 Feb 12.
BACKGROUND/AIMS: G73A polymorphism in the CST3 gene of cystatin C has been associated with Alzheimer's disease, age-related macular degeneration, and cardiovascular disease. However, studies investigating the influence of this genetic variability on serum cystatin C and cystatin-based renal function estimate are limited. Therefore, the aim of this study is to investigate the possible association of single-nucleotide polymorphism (rs1064039) of the CST3 gene on the serum cystatin C level and cystatin C-based estimated glomerular filtration rate (eGFR).
Study subjects include patients with various levels of renal function recruited from the nephrology clinic and wards of a tertiary hospital. The blood samples collected were analyzed for serum cystatin C and creatinine levels by particle-enhanced turbidimetric immunoassay and kinetic alkaline picrate method, respectively. DNA was extracted using a commercially available kit. -Polymerase chain reaction results were confirmed by direct DNA Sanger sequencing.
The genotype percentage (G/G = 73%, G/A = 24.1%, and A/A = 2.9%) adhere to the Hardy-Weinberg equilibrium. The dominant allele found in our population was CST3 73G allele (85%). The regression lines' slope of serum cystatin C against creatinine and cystatin C-based eGFR against creatinine-based eGFR, between G and A allele groups, showed a statistically significant difference (z-score = 3.457, p < 0.001 and z-score = 2.158, p = 0.015, respectively). Patients with A allele had a lower serum cystatin C level when the values were extrapolated at a fixed serum creatinine value, suggesting the influence of genetic factor.
Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.
背景/目的：半胱氨酸蛋白酶抑制剂 C（cystatin C）基因 CST3 中的 G73A 多态性与阿尔茨海默病、年龄相关性黄斑变性和心血管疾病有关。然而，研究这种遗传变异对血清胱抑素 C 和基于胱抑素的肾功能估计的影响的研究有限。因此，本研究旨在探讨 CST3 基因单核苷酸多态性（rs1064039）对血清胱抑素 C 水平和基于胱抑素的估计肾小球滤过率（eGFR）的可能影响。
研究对象包括从一家三级医院的肾病诊所和病房招募的各种肾功能水平的患者。采集的血液样本通过颗粒增强比浊免疫测定法和动力学碱性苦味酸法分别分析血清胱抑素 C 和肌酐水平。使用市售试剂盒提取 DNA。聚合酶链反应结果通过直接 DNA Sanger 测序确认。
基因型百分比（G/G = 73%，G/A = 24.1%，A/A = 2.9%）符合 Hardy-Weinberg 平衡。我们人群中的优势等位基因是 CST3 73G 等位基因（85%）。血清胱抑素 C 与肌酐和基于胱抑素的 eGFR 与基于肌酐的 eGFR 之间的回归线斜率在 G 和 A 等位基因组之间存在统计学差异（z 分数= 3.457，p < 0.001 和 z 分数= 2.158，p = 0.015）。当固定血清肌酐值外推时，具有 A 等位基因的患者血清胱抑素 C 水平较低，表明遗传因素的影响。
CST3 基因 G73A 多态性的存在会影响血清胱抑素 C 水平。
