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Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
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Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
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Journal Article
Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
2021
Overview
In the current study,
APOB
(
rs1052031)
genotype-guided proteomic analysis was performed in a cohort of Pakistani population. A total of 700 study subjects, including Coronary Artery Disease (CAD) patients (n = 480) and healthy individuals (n = 220) as a control group were included in the study. Genotyping was carried out by using tetra primer-amplification refractory mutation system-based polymerase chain reaction (T-ARMS-PCR) whereas mass spectrometry (Orbitrap MS) was used for label free quantification of serum samples. Genotypic frequency of GG genotype was found to be 90.1%, while 6.4% was for GA genotype and 3.5% was for AA genotypes in CAD patients. In the control group, 87.2% healthy subjects were found to have GG genotype, 11.8% had GA genotype, and 0.9% were with AA genotypes. Significant (
p
= 0.007) difference was observed between genotypic frequencies in the patients and the control group. The rare allele AA was found to be strongly associated with the CAD [OR: 4 (1.9–16.7)], as compared to the control group in recessive genetic model (
p
= 0.04). Using label free proteomics, altered expression of 60 significant proteins was observed. Enrichment analysis of these protein showed higher number of up-regulated pathways, including phosphatidylcholine-sterol
O
-acyltransferase activator activity, cholesterol transfer activity, and sterol transfer activity in AA genotype of
rs562338
(G>A) as compared to the wild type GG genotype. This study provides a deeper insight into CAD pathobiology with reference to proteogenomics, and proving this approach as a good platform for identifying the novel proteins and signaling pathways in relation to cardiovascular diseases.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/61
/ Adult
/ Aged
/ Apolipoprotein B-100 - genetics
/ Coronary Artery Disease - genetics
/ Coronary Artery Disease - metabolism
/ Coronary Artery Disease - pathology
/ Female
/ Genetic Predisposition to Disease
/ Genotype
/ Humanities and Social Sciences
/ Humans
/ Lecithin
/ Male
/ Phosphatidylcholine-sterol O-acyltransferase
/ Polymorphism, Single Nucleotide
/ Science
/ Sterols
