Characterization of LDLR rs5925 and PCSK9 rs505151 genetic variants frequencies in healthy subjects from northern Chile: Influence on plasma lipid levels

Abstract

BackgroundIdentification and characterization of genetic variants and their effects on human health may allow to establish relationships between genetic background and susceptibility to developing cardiovascular diseases. LDLR and PCSK9 polymorphisms have been associated with higher lipid levels and risk of cardiovascular diseases. Thus, the main aim of this study was to evaluate genotype distribution and relative allelic frequency of LDLR rs5925 (1959C > T) and PCSK9 rs505151 (23968 A > G) genetic variants and their effects on lipid levels of healthy subjects from northern Chile.MethodsA total of 178 healthy individuals were recruited for this study. The genotyping of rs5925 (LDLR) and rs505151 (PCSK9) polymorphisms was performed by PCR‐RFLP and qPCR, respectively. In addition, glucose and lipid levels were determined and associated with the genetic data.ResultsGenotype distribution for LDLR rs5925 polymorphism was as follows: CC = 19%; CT = 53%; and TT = 28% (HWE: χ 2 = 0.80; P = .37), and for PCSK9 rs505151 genetic variant was as follows: AA = 93%; AG = 7%; and GG = 0% (HWE: χ 2 = 0.22; P = .64). The frequency of T (rs5925) and G (rs505151) mutated alleles was 0.55 and 0.03, respectively. Data showed that individuals carrying LDLR mutated allele (T) presented lower values of total cholesterol, triglycerides, and LDL‐cholesterol when compared to CC homozygous genotype (P < .05). Subgroup analysis revealed that women carrying the PCSK9 mutated allele (G) exhibited higher values of total cholesterol, triglycerides, HDL‐C, and LDL‐C when compared to male group carrying the same genotype (P < .05).ConclusionsThe effect of LDLR rs5925 and PCSK9 rs505151 gene polymorphisms on lipid levels is associated with gender among healthy subjects from northern Chile.

Single Nucleotide Polymorphisms in Apolipoprotein B, Apolipoprotein E, and Methylenetetrahydrofolate Reductase Are Associated With Serum Lipid Levels in Northern Chilean Subjects. A Pilot Study

“…The differences observed in ApoE and MTHFR rs1801133 allelic frequencies in individuals from the northern region of Chile compared with other regions might be explained based on the genetic background of Chilean people as a consequence of some miscegenation events where larger European and Native-American and smaller African ancestry contributed to admixing, showing that African ancestry contribution is higher in the northern region (3.9%) and diminished in southern regions (1.6%), while European ancestry contribution is higher in the central region and Native-American ancestry prevails in the southern region ( Fuentes et al, 2014 ; Ruiz-Linares et al, 2014 ; Eyheramendy et al, 2015 ). Altogether, these observations indicate that the genetic background of Chilean subjects is unevenly spread throughout the country, and this could explain why the studied allelic variants exhibited a geographic dependent pattern as was previously demonstrated for LDLR and PCSK9 polymorphisms ( Rojas et al, 2019 ).…”

Genetics of severe hypercholesterolemia in the general population: Insights from the STANISLAS cohort

“…The variant rs1367117 had already been previously associated with higher concentrations of LDLc 20 . Furthermore, some SNPs located on PCSK9 gene, which did not reach the statistically significant threshold in our study, are known for their associations with LDLc [21][22][23][24][25] .…”

Role of low-density lipoprotein receptor rs5925 (1959C>T) gene polymorphism in pathogenesis of dyslipidemia among Egyptian lupus nephritis patients

“…The current study is the first citation of this gene polymorphism among lupus nephritis patients; however, previous studies reported its prevalence in normal subjects and other pathological conditions. Rojas et al[ 13 ] reported that the frequency of T allele was higher than C allele reaching 55% among healthy individuals. Similarly, Ríos-González et al[ 21 ] reported that the prevalence of the T allele in normal subjects and hypertensive patients were 53.1% and 54.7%, respectively.…”

“…[ 9 , 10 ] All these discrepancies may be due to the prevalence of the mutant allele in different ethnicities and its varying impact on the incidence of dyslipidemia. [ 12 , 13 ] However, the precise role of this gene polymorphism in development of dyslipidemia in lupus nephritis patients remains to be elucidated. Therefore, in the present study, we aimed to investigate the prevalence of LDLR rs5925 gene polymorphism among lupus nephritis patients and to evaluate the effect of these genetic variants on plasma lipid phenotypes, kidney functions, and disease activity.…”