Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs

Jovana Kuveljic; Tamara Djuric; Goran Stankovic; Milica Dekleva; Aleksandra Stankovic; Dragan Alavantic; Maja Zivkovic

doi:10.1016/j.gene.2021.145428

Association of PHACTR1 intronic variants with the first myocardial infarction and their effect on PHACTR1 mRNA expression in PBMCs

Gene. 2021 Apr 5:775:145428. doi: 10.1016/j.gene.2021.145428. Epub 2021 Jan 16.

Authors

Jovana Kuveljic¹, Tamara Djuric², Goran Stankovic³, Milica Dekleva⁴, Aleksandra Stankovic⁵, Dragan Alavantic⁶, Maja Zivkovic⁷

Affiliations

¹ Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: jovana@vin.bg.ac.rs.
² Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: tamariska@vin.bg.ac.rs.
³ Cardiology Clinic, Clinical Center of Serbia, Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
⁴ Faculty of Medicine, University of Belgrade, Belgrade, Serbia; Department of Cardiology, University Clinical Center "Zvezdara", Belgrade, Serbia.
⁵ Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: alexas@vin.bg.ac.rs.
⁶ Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: adragan@vin.bg.ac.rs.
⁷ Laboratory for Radiobiology and Molecular Genetics, "Vinca" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia. Electronic address: majaz@vin.bg.ac.rs.

PMID: 33460763
DOI: 10.1016/j.gene.2021.145428

Abstract

Background: Myocardial infarction (MI) and underlining atherosclerosis are the main causes of death worldwide. Phosphatase and actin regulator 1 (PHACTR1) variants have been associated with early onset MI, coronary artery disease and carotid dissection. PHACTR1 mRNA expression has been detected in tissues and cells related to atherosclerosis. Nonetheless, the true effect of PHACTR1 on vascular diseases is still unknown. Our aim was to examine the association of PHACTR1 intronic variants, rs9349379, rs2026458 and rs2876300, with MI and multi-vessel disease (MVD) and to assess their effect on PHACTR1 and EDN1 mRNA expression in PBMCs of patients six months after MI.

Methods: The study enrolled 537 patients with the first MI and 310 controls. Gene expression was assessed in 74 patients six months after MI and 37 healthy controls. Rs9349379, rs2026458, rs2876300 and relative mRNA expressions were detected by TaqMan® technology.

Results: The significant association between PHACTR1 variants and MI was not found, either individually or in haplotype. A higher frequency of rs2876300G-allele in MVD was rendered not significant after Bonferroni correction. PHACTR1 mRNA was significantly increased in PBMCs of patients six months after MI compared to controls (p = 0.02). Patients that carry ACG haplotype have increased PHACTR1 mRNA expression in PBMCs (p = 0.04). There was no effect of PHACTR1 variants on EDN1 mRNA expression.

Conclusion: Our findings suggest that PHACTR1 intronic variants may have a role in severity and progression of coronary atherosclerosis. Future research is needed to clarify the mechanism underlying the role of PHACTR1 in coronary atherosclerosis and MI.

Keywords: Myocardial infarction; PBMCs; PHACTR1variants; mRNA expression.

MeSH terms

Adult
Age of Onset
Aged
Case-Control Studies
Endothelin-1 / genetics
Female
Genetic Association Studies
Humans
Introns
Male
Microfilament Proteins / genetics*
Middle Aged
Myocardial Infarction / genetics*
Polymorphism, Single Nucleotide*
Severity of Illness Index
Up-Regulation*

Substances

Endothelin-1
Microfilament Proteins
PHACTR1 protein, human