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. 2023 Apr 5:10:1096514.
doi: 10.3389/fcvm.2023.1096514. eCollection 2023.

Association polymorphism of guanine nucleotide-binding protein β3 subunit (GNB3) C825T and insertion/deletion of the angiotensin-converting enzyme (ACE) gene with peripartum cardiomyopathy

Ivana Purnama Dewi  1   2 , Louisa Fadjri Kusuma Wardhani  1 , Irma Maghfirah  1 , Kristin Purnama Dewi  2   3 , Agus Subagjo  1 , Mochamad Yusuf Alsagaff  1 , Johanes Nugroho  1
Affiliations

Association polymorphism of guanine nucleotide-binding protein β3 subunit (GNB3) C825T and insertion/deletion of the angiotensin-converting enzyme (ACE) gene with peripartum cardiomyopathy

Ivana Purnama Dewi et al. Front Cardiovasc Med. .

Abstract

Introduction: Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy-related heart disease. Genetic roles such as gene polymorphisms may relate to the etiology of PPCM. This study analyzes the association between single nucleotide gene polymorphism (SNP) guanine nucleotide-binding protein beta-3 subunit (GNB3) C825T and insertion/deletion (I/D) of the angiotensin-converting enzyme (ACE) gene with the incidence of PPCM.

Methods: An analytic observational study with a case-control design was conducted at the Integrated Cardiac Service Center of Dr. Soetomo General Hospital, Surabaya, Indonesia. PPCM patients of the case and control groups were enrolled. Baseline characteristic data were collected and blood samples were analyzed for SNP in the GNB3 C825T gene and for I/D in the ACE gene by using the polymerase chain reaction, restriction fragment length polymorphism, and Sanger sequencing. We also assessed ACE levels among different ACE genotypes using a sandwich-ELISA test.

Results: A total of 100 patients were included in this study, with 34 PPCM cases and 66 controls. There were significant differences in GNB3 TT and TC genotypes in the case group compared with that in the control group (TT: 35.3% vs. 10.6%, p = 0.003; TC: 41.2% vs. 62.5%, p = 0.022). The TT genotype increased the risk of PPCM by 4.6-fold. There was also a significant difference in the ACE DD genotype in the case group compared with that in the control group (26.5% vs. 9.1%, p = 0.021). DD genotypes increased the risk of PPCM by 3.6-fold. ACE levels were significantly higher in the DD genotype group than in the ID and II genotype groups (4,356.88 ± 232.44 pg/mL vs. 3,980.91 ± 77.79 pg/mL vs. 3,679.94 ± 325.77 pg/mL, p < 0.001).

Conclusion: The TT genotype of GNB3 and the DD genotype of the ACE are likely to increase the risk of PPCM. Therefore, these polymorphisms may be predisposing risk factors for PPCM incidence. ACE levels were significantly higher in the DD genotype group, which certainly had clinical implications for the management of PPCM patients in the administration of ACE inhibitors as one of the therapy options.

Keywords: PPCM; angiotensin-converting enzyme; guanine nucleotide–binding protein subunit β3; peripartum cardiomyopathy; single nucleotide polymorphism.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Visualization of GNB3 PCR products. The results from 10 samples show TT genotypes: sample nos. 2 and 27; CC genotypes: sample nos. 5 and 18; TC genotypes: sample nos. 9, 11, 12, 14, 17, and 25. (B) DNA sequencing chromatogram and amino acid sequence restriction of GNB3. The lines point to nucleotide 825. Chromatogram of GNB3 shows TC genotypes at the upper left, TT genotypes at the upper right, and CC genotypes at the middle bottom. (C) Visualization of ACE gen PCR products. The results from 10 samples show DD genotypes: sample nos. 21, 37, 43, and 50; II genotypes: sample nos. 54 and 55; TC genotypes: sample nos. 26, 30, 49, and 53. GNB3, guanine nucleotide–binding protein beta-3 subunit; PCR, polymerase chain reaction; ACE, angiotensin-converting enzyme.
Figure 2
Figure 2
Comparison of ACE levels among the genotypes of the I/D ACE gene. ACE, angiotensin-converting enzyme; I/D, insertion/deletion.
See this image and copyright information in PMC

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