I/D Polymorphism Gene ACE and Risk of Preeclampsia in Women with Gestational Diabetes Mellitus

Abstract

Preeclampsia (PE) and gestational diabetes mellitus (GDM) are the most common complications of pregnancy, which result in adverse outcomes for the mother and the fetus. GDM is regarded as a separate independent risk factor for PE development, as evidenced by a higher preeclampsia rate in gestational diabetes mellitus than in the general population. The role the endothelial cell dysfunction plays is considered to be the most reasonable one in the origin of these diseases. The activity of plasma and tissue angiotensin converting enzyme (ACE) is believed to be genetically controlled. The available data suggests that increased ACE activity due to deletion (D)/insertion (I) in the 16th intron of ACE gene, which is called ACE gene I/D polymorphism, is associated with preeclampsia and varies depending on the studied population and the geography. We did not find any literature data that estimates the influence of ACE gene I/D polymorphism on PE rate in pregnant women with GDM. Therefore, the present study aimed to investigate a relationship between ACE gene I/D polymorphism and preeclampsia development in the case of GDM in the Russian population. The study used the genomic DNA derived by phenol-chloroform extraction method from venous blood samples in 137 pregnant women, including samples of 74 women with GDM accompanied with PE and the blood samples of 63 women with GDM w/o preeclampsia. Genotyping of insertion/deletion in the I/D region (16 intron of АСЕ gene) was conducted by real-time PCR using the TaqMan competing probe technology. The particular features in the frequency array of alleles and genotypes of the ACE gen I/D polymorphism under review, as associated with preeclampsia development risk in pregnant women with GDM, were identified. The acquired data testify to the need to further study of ACE gene I/D region polymorphism association in a large patient sample taking into account the PE and GDM risk factors estimated in the clinical practice.

Gestational Diabetes Mellitus and Preeclampsia: Correlation and Influencing Factors

“…Some studies suggest that TNF-α, IL-6, and C-reactive protein (CRP) are independent risk factors for PE in women with GDM ( 94 , 175 , 176 ), and others suggest that in addition to the increased level of CRP, the imbalance of Interleukin-17 /Interleukin-35 may also be involved in the pathogenesis of GDM complicated with PE ( 177 ). Genetic variants are also associated with PE in women with GDM, the MIR146Ars2910164CC genotype, HNF1αgene p. I27L TT genotype, and ACE I / D polymorphism DD genotype was significantly higher in women with GDM complicated with PE ( 178 – 180 ). Obesity is the main influencing factor of PE in women with GDM in this paper.…”

Association of the rs4646994 in ACE gene with susceptibility to tuberculosis in a region of the Brazilian Amazon

“…Similar findings were described by Gomez et al, who found that the ACE Del/Del polymorphism was statistically higher in the severe COVID-19 group than in the mild disease group [ 6 ]. Furthermore, Dmitrenko et al found that the Del/Del genotypes were associated with increased risk of pregnancy complication in gestational diabetes mellitus women, increasing its risk by 2,96 [ 11 ]. Zmorzynski et al observed the association between Del/DEl genotype and more than 2-fold risk of multiple myeloma [ 34 ].…”

“…The genotype and allele frequency of this polymorphism has been reported to be associated with several diseases including COVID-19 [ 10 ], cardiovascular disease [ 11 ], cancer [ 12 ], and diabetes mellitus and renal disease [ 13 ] in humans. In the present study, we aim to evaluate the association between ACE (Ins/Del) polymorphism and risk of tuberculosis in an admixture population such as the Brazilian population.…”

Endothelial Dysfunction in Pregnancy Complications

“…ACE gene I/D polymorphism is associated with increased PE risk in the general population. Dmitrenko et al postulated that this polymorphism also elevates the risk of PE in patients with GDM [ 160 ].…”