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Association of ACE I/D and PAI-1 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus

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Abstract

Background

A number of studies were carried out to assess the association of angiotensin I converting enzyme (ACE) I/D and plasminogen activator inhibitor-1 (PAI-1-1) 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus (T2DM). However, there are a few studies in Iranian patients with T2DM. Here, we tested for an association of ACE I/D and PAI-1 4G/5G polymorphisms with T2DM risk.

Methods

One hundred-eighteen patients with T2DM and 125 healthy subjects were participates in this study. The ACE I/D (rs4340) and PAI-1 4G/5G (rs1799889) polymorphisms was genotyped by conventional and PCR–RFLP assays, receptively. The associations was evaluated by calculating the odds ratio (OR) and 95% confidence interval (95% CI).

Results

The genotype distribution of ACE I/D and PAI-1 4G/5G polymorphisms were not deviated from the Hardy–Weinberg equilibrium in healthy controls. The ACE II, ID, and DD genotype frequencies were 18.6%, 48.3%, and 33.1% in the T2DM patients versus 24.0%, 45.6% and 30.4% in healthy subjects, respectively. The PAI-1 4G/4G, 4G/5G, and 5G/5G genotype frequencies were 16.9%, 51.7%, and 31.4% in cases versus 24.8%, 57.6% and 17.6% in controls, respectively. There is a significant distribution in genotype/allele of PAI-1 4G/4G between cases with T2DM and healthy control, but not for ACE I/D. Moreover, the 5G/5G genotype is significantly (OR = 2.139, CI 95% 1.171–3.907, p = 0.013) increased the risk of T2DM by two folds in the cases than healthy controls.

Conclusions

Our findings suggest that PAI-1 4G/5G may be likelihood risk factor for the development of T2DM in the Iranian patients. The higher frequency of PAI-1 5G/5G genotype in patients with T2DM revealed that individuals with the 5G allele may be at higher risk of T2DM development than those with 4G. However, there was no significant association between ACE I/D polymorphism and T2DM in our population. Future rigorous, well-designed studies with larger sample should replicate this study to confirm our findings in Iranian T2DM patients.

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Data availability

The datasets generated during and/or analyzed during this study are the corresponding author on reasonable request.

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Funding

This study was performed by individual funding grants.

Author information

Authors and Affiliations

  1. Department of Biology, Ashkezar Branch, Islamic Azad University, Ashkezar, Iran

    Somaye Miri

  2. Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Mohammad Hasan Sheikhha & Hossein Neamatzadeh

  3. Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Alireza Dastgheib

  4. Department of Anatomy School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Seyed Amir Shaker

  5. Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Hossein Neamatzadeh

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  1. Somaye Miri
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Contributions

SM, MHS and SAD: Methodology, conceptualization.

SM, AS, and HN: investigation.

HN, SM, and SAD: Methodology, software.

MHS, HN, AS: Formal analysis, investigation.

SM, AS, HN and SAD: Writing, reviewing, editing.

Corresponding author

Correspondence to Mohammad Hasan Sheikhha.

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Ethics approval

This study was approved by Ashkezar Branch, Islamic Azad University, Ashkezar, Iran.

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A written informed consent was obtained from each participant.

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The authors declare that they have no conflict of interest.

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Miri, S., Sheikhha, M.H., Dastgheib, S.A. et al. Association of ACE I/D and PAI-1 4G/5G polymorphisms with susceptibility to type 2 diabetes mellitus. J Diabetes Metab Disord 20, 1191–1197 (2021). https://doi.org/10.1007/s40200-021-00839-7

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