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The Association Between rs1748195 and rs11207997 Variants of the ANGPTL3 Gene and Susceptibility to Cardiovascular Disease in the MASHAD Cohort Study

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Abstract

There is a strong genetic predisposition to cardiovascular disease (CVD). Loss-of-function variants of the angiopoietin-like 3 (ANGPTL3) gene have been reported to be associated with several lipid-related CVD risk factors that include serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) level, and total cholesterol (TC). We aimed to determine the association of two genetic variants, rs1748195 and rs11207997, of the ANGPTL3 locus and CVD risk in the Mashhad Stroke and Heart Atherosclerotic Disorders (MASHAD) cohort study. The participants were 1002 individuals in the MASHAD cohort, with or without CVD, during the 6 years of follow-up. The subjects were categorized into two groups according to serum HDL concentration. DNA was extracted by the routine salting-out method, and genotyping of rs1748195 and rs11207997 variants of the ANGPTL3 gene was performed using the ARMS PCR method. Univariate and multivariate statistical analysis was used to assess the two gene variants’ association with incident CVD and baseline lipid profile. There was a significant relationship between rs1748195 GG genotype and CVD risk in the individuals with a normal serum HDL-C. There was a significant association between the CT genotype of the rs11207997 polymorphism and CVD risk in individuals with a low serum HDL-C. Furthermore, carriers of the GG genotype of the rs1748195 and CT genotype of rs11207997 variant of ANGPTL3 had a higher risk of developing CVD disease. We have shown that the 1748195(GG) and 11207997(CT) gene variants of the ANGPTL3 locus are associated with an increased risk of CVD in an Iranian population sample.

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Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

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Acknowledgements

We gratefully acknowledge the contributions of the data collection team and the individuals who participated in this study. This project was implemented in collaboration with the Cardiovascular Diseases Research Center in Birjand and Mashhad University of Medical Sciences. We thank Dr. Tooba Kazemi and Dr. Ebrahim Miri-Moghaddam (Cardiovascular Diseases Research Center, Birjand), and Dr. Majid Ghayour Mobarhan (Iranian UNESCO center of excellence for human nutrition) for guidance in our project.

Funding

This work was supported by Birjand University of Medical Science (Tooba Kazemi) and Mashhad University of Medical Science (Habibollah Esmaily), Iran.

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Author notes

  1. Ebrahim Miri-Moghaddam and Majid Ghayour-Mobarhan have contributed equally to this work.

Authors and Affiliations

  1. Student Research Committee, Department of Molecular Medicine, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

    Malihe Aghasizadeh

  2. Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Hamideh Safarian, Mohamad Haqhani & Amir Avan

  3. Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Avan

  4. Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran

    Malihe Aghasizadeh, Tooba Kazemi & Ebrahim Miri-Moghaddam

  5. Razi Clinical Research Development Unit (RCRDU), Birjand University of Medical Sciences, Birjand, Iran

    Tooba Kazemi

  6. Division of Medical Education, Brighton & Sussex Medical School, Falmer, Brighton, BN19PH, Sussex, UK

    Gordon A. Ferns

  7. Department of Epidemiology and Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran

    Habibollah Esmaily

  8. Biochemistry of Nutrition Research Center, School of Medicine, Iranian UNESCO Center of Excellence for Human Nutrition, Mashhad University of Medical Sciences, 99199-91766, Mashhad, Iran

    Majid Ghayour-Mobarhan

Authors
  1. Malihe Aghasizadeh
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  2. Hamideh Safarian
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  3. Mohamad Haqhani
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  7. Habibollah Esmaily
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  8. Ebrahim Miri-Moghaddam
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  9. Majid Ghayour-Mobarhan
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Contributions

We declare that we contributed significantly toward the research study; MA, TK, EMM, MGM, and AA designed the experiments and revised the manuscript. MA and MH performed the experiments. MA, HS, and GF wrote the manuscript. MA, HE carried out the data analysis. All authors reviewed, considered, and approved the manuscript.

Corresponding authors

Correspondence to Ebrahim Miri-Moghaddam or Majid Ghayour-Mobarhan.

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Conflict of interest

The authors have no conflict of interest to disclose.

Ethical Approval

Informed consent was obtained from all subjects using protocols approved by the Ethics Committee of the Mashhad University of Medical Sciences (IR. MUMS. Medical. rec. 1386.250) and the Ethics Committee of the Birjand University of Medical Science (IR.bums.rec.1398.51).

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Aghasizadeh, M., Safarian, H., Haqhani, M. et al. The Association Between rs1748195 and rs11207997 Variants of the ANGPTL3 Gene and Susceptibility to Cardiovascular Disease in the MASHAD Cohort Study. Biochem Genet 60, 738–754 (2022). https://doi.org/10.1007/s10528-021-10122-2

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  • DOI: https://doi.org/10.1007/s10528-021-10122-2

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