Abstract

Analysis of nonsynonymus single nucleotide polymorphism rs1468384 of Niemann-Pick C1-Like 1 gene and its association with serum cholesterol levels in Nepalese population

Author(s): K.P.Singh, U.Timilsina, H.K.Tamang, P.Yadav4, B.Gautam, S.Shrestha, I.Shrestha, S.Khadka

Background: Niemann-Pick C1-Like 1 protein is a newly identified sterol influx transporter actively involved in the cholesterol homeostasis pathway. Nonsynonymus Single Nucleotide Polymorphism rs1468384 (GA transition) shows decrease in the stability of the protein as analysed in silico by MuPro software. Related data on allelic frequency and the effect of this polymorphism on the serum cholesterol levels in Nepalese population are not available. This study aims to detect rs1468384 in Nepalese population using the Polymerase Chain Reaction – Restriction Fragment Length Polymorphism technique, determine the allelic frequency of this polymorphism and to correlate it with the serum cholesterol level. Materials and Methods: A total number of 74 healthy human subjects were randomly selected within Kathmandu valley. DNA was isolated from blood leukocytes. Polymerase Chain Reaction – Restriction Fragment Length Polymorphism technique was used to identify the genotypes. Lipid profile analysis was performed using cholesterol oxidase peroxidae (CHOD-PAP) method (systemic reagent of Humastar 600, Human, Germany). Results: Genotype distribution was in accordance with Hardy-Weinberg Equilibrium (X2=2.0233, df=1). ‘G’ allele frequency (p=0.8581) was higher than the mutated ‘A’ allele (q=0.1419) in Nepalese population. Genotype frequency distribution among Gender was not statistically significant (p value =0.427). Statistically significant differences in Total Cholesterol Level and LDL Cholesterol Level between genotypes were observed (Total Cholesterol Level “Genotype GG” 160.7 ± 30.3 mg/dl; “Genotype AG” 145.1 ± 22.5 mg/ dl, p value =0.019 and LDL Cholesterol Level “Genotype GG” 99.9 ± 28.6 mg/dl; “Genotype AG” 84.7 ± 19.3 mg/dl, p value =0.011). Conclusion: Relatively higher prevalence of rs1468384 polymorphism among Nepalese population was found in this study. The study showed a strong association between this polymorphism and the serum cholesterol levels.