Abstract
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.
Highlights
In the current study, Apolipoprotein B gene (APOB) genotype-guided proteomic analysis was performed in a cohort of Pakistani population
Recent studies have shown that ApoB concentration provides direct measure of the total lipoproteins (LDL, low density lipoprotein (LDL) remanats, Lp(a)) that leads to atherosclerosis, as every single atherogenic particle comprised of one molecule of ApoB inside[9]
Anthropometric and clinical parameters such as Body mass index (BMI), waist-to-hip ratio (WHR), blood glucose, and blood pressure were significantly higher (p < 0.05) in the disease group when compared to the control group
Summary
APOB (rs1052031) genotype-guided proteomic analysis was performed in a cohort of Pakistani population. Recent studies have shown that ApoB concentration provides direct measure of the total lipoproteins (LDL, LDL remanats, Lp(a)) that leads to atherosclerosis, as every single atherogenic particle comprised of one molecule of ApoB inside[9]. It is a well-known risk factor for hyperlipidemia, and its deficiency leads to h ypobetalipoproteinemia[10,11]. According to the European Society of Cardiology (ESC), and European Atherosclerosis Society (EAS), during the atherosclerotic cardiovascular disease (ASCVD) risk assessment, ApoB evaluation is preferred over the measurement of LDL-cholesterol in patients with hypertriglyceridemia, obesity, and diabetes, as it provides a better and direct measure of a therosclerosis[14]. Proteogenomics, the integration of genomics and proteomics data has become very popular for identifying novel proteins or signaling pathways in relation to various d iseases[23]
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