Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach

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 st...

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Autores principales:	Muneeza Zafar, Munazza Raza Mirza, Fazli Rabbi Awan, Muhammad Tahir, Rabia Sultan, Misbah Hussain, Ahmed Bilal, Shahid Abbas, Martin R. Larsen, Muhammad Iqbal Choudhary, Imran Riaz Malik
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/307672411bb2458cbf0c74259e91c06c
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spelling	oai:doaj.org-article:307672411bb2458cbf0c74259e91c06c2021-11-28T12:18:53ZEffect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach10.1038/s41598-021-02211-42045-2322https://doaj.org/article/307672411bb2458cbf0c74259e91c06c2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-02211-4https://doaj.org/toc/2045-2322Abstract 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.Muneeza ZafarMunazza Raza MirzaFazli Rabbi AwanMuhammad TahirRabia SultanMisbah HussainAhmed BilalShahid AbbasMartin R. LarsenMuhammad Iqbal ChoudharyImran Riaz MalikNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Muneeza Zafar Munazza Raza Mirza Fazli Rabbi Awan Muhammad Tahir Rabia Sultan Misbah Hussain Ahmed Bilal Shahid Abbas Martin R. Larsen Muhammad Iqbal Choudhary Imran Riaz Malik Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
description	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.
format	article
author	Muneeza Zafar Munazza Raza Mirza Fazli Rabbi Awan Muhammad Tahir Rabia Sultan Misbah Hussain Ahmed Bilal Shahid Abbas Martin R. Larsen Muhammad Iqbal Choudhary Imran Riaz Malik
author_facet	Muneeza Zafar Munazza Raza Mirza Fazli Rabbi Awan Muhammad Tahir Rabia Sultan Misbah Hussain Ahmed Bilal Shahid Abbas Martin R. Larsen Muhammad Iqbal Choudhary Imran Riaz Malik
author_sort	Muneeza Zafar
title	Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
title_short	Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
title_full	Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
title_fullStr	Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
title_full_unstemmed	Effect of APOB polymorphism rs562338 (G/A) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
title_sort	effect of apob polymorphism rs562338 (g/a) on serum proteome of coronary artery disease patients: a “proteogenomic” approach
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/307672411bb2458cbf0c74259e91c06c
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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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