Nor Asyikin Mohd Tahir1, Shamin Mohd Saffian1, Farida Hanim Islahudin1, Abdul Halim Abdul Gafor2, Hanita Othman3, Hamizah Abdul Manan3, Mohd Makmor-Bakry4. 1. Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. 2. Nephrology Unit, Department of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia. 3. Department of Pathology, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia. 4. Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia, mohdclinpharm@ukm.edu.my.
Abstract
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). METHODS: 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. RESULTS: 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. CONCLUSION: Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.
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). METHODS: 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. RESULTS: 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. CONCLUSION: Presence of CST3 gene G73A polymorphism affects serum cystatin C levels.
Authors: Fei Yee Lee; Farida Islahudin; Aina Yazrin Ali Nasiruddin; Abdul Halim Abdul Gafor; Hin-Seng Wong; Sunita Bavanandan; Shamin Mohd Saffian; Adyani Md Redzuan; Nurul Ain Mohd Tahir; Mohd Makmor-Bakry Journal: J Pers Med Date: 2021-03-30