Association of ACE*(Insertion/Deletion) Variant with the Elevated Risk of Preeclampsia Among Gestational Women

Eman Fawzy El Azab; Rabab Gad Abd El-Kader; Thoraya Mohamed Elhassan; Sameh A Mohammed Ali; Esraa Ibrahim A Shaaban; Mohamed Adel El-Eshmawy; Dina Abdel Hamid; Nanis S El-Beltagy; Eman T Salem; Afaf M Elsaid; Mohamed I Elsalahaty; Rami M Elshazli; Nahla Anber

doi:10.1007/s10528-023-10620-5

Association of ACE*(Insertion/Deletion) Variant with the Elevated Risk of Preeclampsia Among Gestational Women

Biochem Genet. 2024 Jan 14. doi: 10.1007/s10528-023-10620-5. Online ahead of print.

Authors

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia.
² Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
³ Community Health Nursing Department, RAK College of Nursing, RAK Medical and Health Science University, Ras Al-Khaimah, United Arab Emirates.
⁴ Community Health Nursing Department, Faculty of Nursing, Mansoura University, Mansoura, Egypt.
⁵ Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt.
⁷ Department of Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
⁸ Department of Clinical Pathology, Mansoura University Hospital, Mansoura, Egypt.
⁹ Hematology and Bone Marrow Transplant Unit, Children's University Hospital, Mansoura University, Mansoura, Egypt.
¹⁰ Department of Laboratories, Faculty of Medicine, Children's University Hospital, Mansoura University, Mansoura, Egypt.
¹¹ Department of Basic Sciences, Faculty of Physical Therapy, Horus University-Egypt, New Damietta, 34518, Egypt.
¹² Genetic Unit, Children's University Hospital, Mansoura University, Mansoura, Egypt.
¹³ Biochemistry Division, Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
¹⁴ Biochemistry and Molecular Genetics Unit, Department of Basic Sciences, Faculty of Physical Therapy, Horus University-Egypt, New Damietta, 34518, Egypt. Relshazly@horus.edu.eg.
¹⁵ Emergency Hospital, Mansoura University, Mansoura, Egypt.

PMID: 38219243
DOI: 10.1007/s10528-023-10620-5

Abstract

The renin-angiotensin-aldosterone system has an indispensable function in the uteroplacental circulation, placental growth, and blood pressure optimization. The angiotensin I converting enzyme (ACE) gene is a critical integrator for electrolyte balance, and water retention, along with inhibiting preeclampsia. The main goal of this pertaining study is to assess the contribution of ACE*(Ins/Del) variant with the susceptibility for preeclampsia with focus on the severity of the disease among gestational hypertensive women. This retrospective study included 225 participants [125 PE gestational women, and 100 normotensive healthy controls] matching with age, and geographical region. PE women classified into 82 early-onset PE women, accompanied with 43 late-onset PE women. Additionally, PE women categorized into 59 mild PE women, together with 66 severe PE women. The genotyping and characterization of ACE*(Ins/Del) variant were applied using the PCR technique. Our findings indicated higher frequency of the ACE*(Del/Del) genotype and ACE*(D allele) with elevated risk of preeclampsia compared to normotensive controls under recessive (OR = 2.09, and p-value = 0.007), and allelic (OR = 1.75, and p-value = 0.012) models. In addition, testing logistic regression revealed that the levels of endothelin-1 and malondialdehyde exposed significant difference for the ACE*(Del/Del) genotype among early-onset and late-onset PE women (p-value = 0.024, and 0.23, respectively). Furthermore, carriers of the ACE*(Del/Del) genotype observed statistically significant with lower sodium concentrations among severe PE women (p-value = 0.034). The ACE*(Del/Del) genotype and ACE*(D allele) were associated with increased risk preeclampsia among gestational women. Furthermore, early-onset PE and late-onset PE were correlated with endothelin-1 and malondialdehyde concentrations among Egyptian women.

Keywords: ACE*(Ins/Del) variant; Genetic variants; Gestational hypertension; Preeclampsia; RAAS.