Low-density Lipoprotein Receptor-related Protein 8 Gene Research Articles

A substitution mutation in LRP8 gene is significantly associated with susceptibility to familial myocardial infarction.

BACKGROUNDMyocardial infarction (MI) is a multifactorial disease caused by the suspension of blood circulation in a part of the myocardium. Understanding the genetic basis of MI can provide insight regarding the pathogenesis of the disease. The aim of this study was to investigate the association between pathogenic mutations and early-onset MI in five families with familial MI and without common MI risk factor.METHODSPatients with MI younger than 50 years with family history of MI and without common diagnostic criteria (obesity, diabetes, familial hypercholesterolemia, opium/alcohol use) were evaluated for pathogenic mutations by whole exome sequencing (WES) and mutation was confirmed by polymerase chain reaction (PCR)-Sanger sequencing.RESULTSThe c.2855G > A missense mutation with homozygous autosomal recessive inheritance was identified in low-density lipoprotein receptor-related protein 8 (LRP8) gene in all patients of a family.CONCLUSIONThe c.2855G > A (R952Q) mutation in LRP8 gene in homozygous state could be considered as a possible etiology of early-onset familial MI.

LRP8 (rs5177) and CEP85L (rs11756438) are contributed to schizophrenia susceptibility in Iranian population

Introduction Schizophrenia is recognized as one of the most important mental illnesses of the last century. Many genetic and environmental factors are involved in this condition. Recently, the genome-wide association study identified two significant genes LRP8 and CEP85L associated with psychiatric disorders. LRP8 (low-density lipoprotein receptor-related protein 8) acts as a cytoplasmic receptor for Reelin. Many studies have revealed that LRP8 was significantly related to schizophrenia and bipolar disorder in Chinese population. CEP85L standing for 'centrosomal protein 85 kDa-like' is another gene, which has been reportedly associated with BPD. Methods We performed a case-control study to analyze the association between rs5177 single-nucleotide polymorphism in the LRP8 gene plus the single-nucleotide polymorphism rs11756438 in the CEP85L gene and schizophrenia in the Iranian population. The genotype for rs5177 was determined by ARMS PCR method, while for rs11756438 genotype, it was determined by PCR-RFLP method after which statistical analysis was performed for each polymorphism. In rs5177, the CC genotype was susceptible to the disease while G allele was associated with disease protection. Results and Conclusion In rs11756438, the AA genotype was associated with disease susceptibility, while allele A did not have a significant association with the disease.

Molecular cloning, expression and polymorphism of goose LRP8 gene

1. The low-density lipoprotein receptor-related protein 8 (LRP8), a member of the low-density lipoprotein receptor (LDLR) gene family, participates in the supplying of lipid during follicular development. The objective of the study was to identify and characterise the LRP8 gene in goose.2. A 2867 bp fragment that covered the complete coding region (CDS) of goose (Anser cygnoides) LRP8 gene was cloned. It encoded a protein of 917 amino acid residues containing a 24-amino acid signal peptide and 5 functional domains. The goose LRP8 showed high nucleic acid and amino acid identities with those in other species.3. Similarly to duck LRP8 gene, two splice variants of LRP8, LRP8-1 (containing 8 ligand-binding repeats) and LRP8-2 (containing 7 ligand-binding repeats), were identified in goose.4. Semi-quantitative RT-PCR analysis indicates that the LRP8-1 transcript is expressed in heart, liver, spleen, lung, kidney, breast muscle, duodenum, hypothalamus, pituitary and ovary, negligible or absent in sebum and oviduct, and the LRP8-2 transcript is widely expressed in all examined tissues.5. A total of 7 SNPs were identified in the coding region of the goose LRP8 gene.

The cloning, characterization, and expression profiling of the LRP8 gene in duck (Anas platyrhynchos)

Low-density lipoprotein receptor-related protein 8 (LRP8) is a member of the low-density lipoprotein receptor gene family that functions in body lipoprotein homeostasis. In this study, reverse transcription-polymerase chain reaction, rapid amplification of cDNA ends, and real-time PCR were performed to characterize the duck LRP8 gene. The cDNA of duck LRP8 contained a 14-bp 5' UTR, a 2754-bp open reading frame, and a 189-bp 3' UTR. The duck LRP8 encoded a protein of 917 amino acid residues composed of five functional domains and resembling other members of the LDLR family, and it displayed high nucleotide and amino acid homology to the LRP8 sequences in other avian species. The mRNA expression level of LRP8 was greater in duck extra-hepatic adipose tissue than in the liver. The peak expression values of LRP8 in both liver and adipose tissues occurred at week 1 and were significantly higher than the values observed during any other week (p < 0.05). Differences in the expression patterns of LRP8 mRNA from weeks 2 to 8 of growth were observed in different organs. A consistent low expression was observed in the liver, and fluctuating expression was observed in the subcutaneous adipose tissue (up- and then down-regulated) and abdominal adipose tissue (down-, then up-, then down-regulated). These findings suggest that LRP8 might play more important roles in regulating lipid metabolism in extra-hepatic adipose tissues than in the liver during early growth after hatching in the duck.

Association analysis of LRP8 SNP rs3820198 and rs5174 with Parkinson’s disease in Han Chinese population

Objectives: The single-nucleotide polymorphism (SNP) rs5174 of the low-density lipoprotein receptor-related protein 8 (LRP8) gene has been linked to decreased risk for Parkinson’s disease (PD) on Caucasian populations. However, this association has not been proven in Han Chinese populations.Methods: A total of 378 unrelated Han patients with PD from the Department of Neurology, West China Hospital of Sichuan University and 274 unrelated Han healthy controls (HCs) from the same region were included in this study. SNPs rs5174 and rs3820198 were genotyped using the Sequenom iPLEX Assay technology.Results: No significant difference was found in the genotype and minor allele frequencies (MAFs) of SNPs rs5174 and rs3820198 between the PD and HC groups, the early-onset PD and HC groups, the late-onset PD and HC groups, as well as the early-onset PD and late-onset PD groups.Conclusion: This report is the first one on the lack of association of the LRP8 SNPs rs5174 and rs3820198 with PD in Han Chinese population. Together with a Japanese study, the results indicate that the variants within the LRP8 gene do not contribute to the risk of developing PD in Asian populations.

Investigation of LRP8 gene in 1p31 QTL linked to LDL peak particle diameter in the Quebec family study

The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on 236 nuclear families of the Quebec Family Study (QFS) revealed a quantitative trait locus affecting LDL peak particle diameter (LDL-PPD) and density on the 1p31 region. This region contains the low-density lipoprotein receptor-related protein 8 (LRP8) gene. LRP8, a receptor for apolipoprotein (apo) E, modulates apoE levels, thus contributing to plasma cholesterol and triglyceride (TG) concentrations. We investigate the effects of LRP8 polymorphisms on LDL-PPD, on the relative proportion of small LDL (< 255 Å) and the absolute concentration of cholesterol among the small LDL particles. LRP8 rs5174 was associated with LDL-PPD and estimated cholesterol concentrations in the small LDL particles adjusted for the effects of age and sex ( p = 0.008, p = 0.04, respectively). LRP8 rs3820198 was associated with total and LDL-cholesterol levels as well as with apoB concentrations adjusted for the effects of age and sex ( p = 0.005, p = 0.004 and p = 0.01, respectively) but not with LDL size-related variables. These results suggest that LRP8 gene polymorphisms influence plasma cholesterol levels as well as size and composition of LDL particles.