The association of renin–angiotensinogen system genes polymorphisms and idiopathic recurrent pregnancy loss

Abstract

The most common complication of pregnancy is idiopathic recurrent pregnancy loss (RPL). To identify the contribution of gene polymorphisms to this condition, we evaluated the association between RPL and the angiotensinogen (AGT), angiotensin receptor 1 (AGTR1) and Angiotensinogen converting enzyme (ACE). In this case-control study, the frequency of AGT (rs4762 and rs699), AGTR1 (rs5186) and ACE insertion/deletion (rs4340) polymorphisms in 202 idiopathic RPL women was compared with 210 women with no history of abortion, using tetra-primer ARMS-PCR. Polymorphisms were analysed by logistic regression analysis according to inheritance models. The CT genotype of AGT rs4762, the CC genotype of AGT rs699 and the AC genotype of AGTR1 rs5186 in a co-dominant inheritance model were associated with idiopathic RPL (OR = 1.63, 95% CI = 1.07-2.49 of CT versus CC; OR = 5.97, 95% CI = 1.28-27.82 of CC versus TT; and OR = 1.99, 95% CI = 1.22-3.07 of AC versus AA). The allele frequency of AGT rs699 and AGTR1 rs5186 polymorphisms, but not AGT rs4762 and ACE rs4340 polymorphisms were significantly different between women with RPL patients and controls (p = 0.020, p = 0.003, p = 0.105 and p = 0.065, respectively). These results show that there is a significant relationship between AGT (rs699) and AGTR1 (rs5186) polymorphisms and idiopathic RPL in the Iranian population.

A meta-analysis of the association of the ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Iranian women: Are the investigations adequate?

“…Subsequently, 75 publications were excluded because they were reviews, previous meta-analyses, and evaluated the association of RPL with other polymorphism of ACE and PAI-1 genes. Finally, a total of 14 studies involving eight studies with 783 patients and 761 controls on the ACE I/D polymorphism ( 6 , 18 , 29 , 32 , 33 , 34 , 35 ) and six studies with 1155 patients and 699 controls on the PAI-1 4G/5G polymorphism ( 18 , 31 , 34 , 36 38 ) were included in this meta-analysis. One study in the present meta-analysis did not state the source of controls.…”

“…The etiology of RPL is complicated, and several risk factors are involved in the development of the disease. In addition to fetal and maternal factors, including chromosomal abnormalities, endocrine and metabolic aberrations, and autoimmune abnormalities, genetic single nucleotide polymorphisms at different loci, also play essential roles in RPL ( 6 , 12 , 39 ) . In this meta-analysis, we evaluated the association of the ACE I/D and PAI-1 4G/5G polymorphisms with RPL risk in Iranian women from all eligible case-control studies.…”

“…RPL is defined as the loss of three or more successive pregnancies before viability and includes all pregnancy losses from the time of conception until 24 weeks of gestation ( 3 , 4 , 5 ) . The most commonly cited causes of miscarriage are structural chromosome abnormalities of one of the partners, uterine abnormalities, elevated random levels of homocysteine, and antiphospholipid syndrome ( 6 , 7 ) . Thrombophilia is described as a susceptibility to arterial or venous thrombotic complications due to hemostatic system defects, which may be acquired, like the antiphospholipid syndrome, or inherited ( 8 , 9 ) .…”

The powerful association of angiotensin-converting enzyme insertion/deletion polymorphism and idiopathic recurrent pregnancy loss

“…Data by several regions demonstrated that the D allele and DD genotype leads to a high PAI-1 level which reduced fibrinolysis and thus correlated with an increased risk of IRPL [9,12,15]. Many studies have been managed to explore the link between ACE I/D polymorphism alleles and genotypes and IRPL, but the results of these studies differ from each other [13][14][15][19][20][21][22][23][24]. Our results showed that the ACE I/D polymorphism was associated with IRPL, and that women that carried DD or ID genotypes had a 72% elevated risk of developing IRPL than women with the II genotype [OR (95% CI): 1.72 (1.181-2.5)].…”

“…Several researches were also conducted to search the possible association with ACE I/D polymorphism and IRPL. The potential role of ACE I/D polymorphism in IRPL pathogenesis has been controversial [3,9,[12][13][14][15].…”