Effects of CST3 Gene G73A Polymorphism on Cystatin C in a Prospective Multiethnic Cohort Study

<b><i>Background/Aims:</i></b> 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). <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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, <i>p</i> &#x3c; 0.001 and z-score = 2.158, <i>p</i> = 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. <b><i>Conclusion:</i></b> Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.