Angiotensin-converting enzyme insertion-deletion polymorphism in normotensive and pre-eclamptic pregnancies

Morgan, Linda; Foster, F. M.; Hayman, Richard; Crawshaw, Sarah; Baker, Philip N.; Pipkin, Fiona Broughton; Kalsheker, Noor

doi:10.1097/00004872-199917060-00007

Cited by 50 publications

(33 citation statements)

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“…Specifically, our data show an increased risk for preeclampsia in women carrying the AGT TT genotype. In accordance to other investigators [18,19] we did not find an association between the ACE ID polymorphism but we noticed an increased OR for women carrying the DD genotype of the ACE gene. To our knowledge, there have been no reports as to whether interaction between specific polymorphisms of the ACE, AGT and AT1R genes has an impact on pregnancy complicated by preeclampsia.…”

Section: Discussionsupporting

confidence: 92%

“…Human linkage and association genetic studies have revealed the presence of polymorphisms in genes encoding key components of the RAS that account for the proportion of the variance in activity of this system [13][14][15]. Studies of these polymorphisms reported both positive [16,17] and negative association with preeclampsia [18,19]. However, although the association of each of these polymorphisms with preeclampsia has been studied extensively, there are no available data of the possible synergistic effect of these variants.…”

Section: Introductionmentioning

confidence: 99%

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Interaction between the polymorphisms of the renin–angiotensin system in preeclampsia

Bouba

Makrydimas

Kalaitzidis

et al. 2003

European Journal of Obstetrics & Gynecology and Reproductiv

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Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the reninangiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P < 0:02). In addition, women with preeclampsia and TT genotype had more frequently the DD genotype or the 1166C allele than the control group showing a significant interaction between the genes. In conclusion, we found an association between the angiotensinogen variant 235T and preeclampsia as well as an interaction between the variant 235T and the two other genes studied. #

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Interaction between the polymorphisms of the renin–angiotensin system in preeclampsia

Bouba

Makrydimas

Kalaitzidis

et al. 2003

European Journal of Obstetrics & Gynecology and Reproductiv

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“…14 Moreover, it has been assumed that the I allele has a sequence similar to a silencer sequence, which might explain why the D allele is associated with higher ACE levels than the I allele. 15 ACE activity and ACE I/D polymorphism were not found to be associated with PE in previous studies, 9,16,17 but no information is available about the effect of this polymorphism on maternal-fetal hemodynamics in women at high risk of PE.…”

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confidence: 85%

Maternal-Fetal Flow, Negative Events, and Preeclampsia

et al. 2003

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Abstract-The risk for an adverse pregnancy outcome is markedly higher in women with history of preeclampsia. This may stem from impaired placentation in early gestation and from high impedance to flow in uteroplacental circulation. The renin-angiotensin system is one of the mediators of the remodeling of spiral arteries throughout pregnancy. The D allele of the Insertion/Deletion (I/D) polymorphism in the ACE gene has been associated with higher ACE activity, accounting for 47% of the total phenotypic variance of serum enzyme levels. To investigate whether the ACE I/D polymorphism affects maternal uteroplacental and fetal umbilical circulation and the pregnancy outcome in women with a history of preeclampsia, 106 women underwent Doppler examination of uterine arteries resistance index and umbilical artery pulsatility index at the 16th, 20th, and 24th weeks of gestation and were genotyped for the I/D polymorphism. This study found a difference in genotype distribution (Pϭ0.0002) and allele frequency (PϽ0.0001) between women with and those without preeclampsia recurrence and fetal growth restriction as well as an association (Pϭ0.0007) between DD genotype and risk of recurrent preeclampsia or fetal growth restriction. At the 16th, 20th, and 24th weeks, uterine artery resistance indexes were significantly lower in II, higher in DD, and intermediate in ID genotype carriers, whereas the umbilical artery pulsatility index values were significantly higher in the DD group in comparison to ID and II genotypes. Key Words: angiotensin-converting enzyme Ⅲ polymorphism Ⅲ preeclampsia Ⅲ pregnancy T he risk for an adverse pregnancy outcome in women who have previously had preeclampsia is markedly higher (from 20% to 40%) 1,2 in comparison to women with history of normal pregnancy, but the mechanisms involved have not yet been identified. The maternal syndrome of preeclampsia (PE) and the fetal syndrome of fetal growth restriction (FGR) during the latter half of pregnancy are believed to result from impaired placentation in early gestation. 3,4 Deficient placentation is characterized by inadequate trophoblast invasion into the maternal spiral arteries and a failure to develop lowresistance uteroplacental circulation. 3 Doppler ultrasonographic studies of uteroplacental 5 and fetal umbilical circulation 6 have shown that high impedance to flow is associated with subsequent PE, FGR, and related complications.Previous experimental studies 7 suggested that the "physiological remodeling" of spiral arteries throughout pregnancy is mediated by the renin-angiotensin system (RAS), which is one of the main factors regulating blood pressure, and fluid and electrolyte balance. 8 Throughout normal pregnancy, the RAS is stimulated; plasma renin activity, angiotensinogen, angiotensin II, and aldosterone levels are all increased. 9 At the same time, pregnancy induces a refractoriness to the pressor effects of angiotensin II. 10 In patients with PE, a significant association between the T235 molecular variant of the angiotensinogen (AGT) gene, ...

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“…Fatini et al [16] found an association of the D/D genotype with first-trimester miscarriages. Recent reports have shown that the ACE D/I polymorphism is even a stronger risk factor for RM than the two better-established thrombophilic mutations FVL and FII G20210A [17,18] .…”

mentioning

confidence: 99%

Polymorphisms in <i>NOS3, ACE </i>and<i> PAI-1</i> Genes and Risk of Spontaneous Recurrent Miscarriage in the Gaza Strip

Sallout

Sharif

2010

Med Princ Pract

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Objective: This study was conducted to investigate the correlation between spontaneous recurrent miscarriage (RM) and common polymorphisms in angiotensin-converting enzyme (ACE), plasminogen activator inhibitor 1 (PAI-1) and endothelium-derived nitric oxide synthase 3 (NOS3) genes among women experiencing RM in the Gaza Strip. Methods: The presence of these genetic profiles was determined for 100 women who had had at least 3 constitutive abortions and 100 controls without any history of abortion using molecular biological techniques. Results: The ACE D/D polymorphism was present in 49% of the study population and in 54% of the controls (p = 0.479). Similarly, there was no significant difference detected in the distribution of polymorphisms for PAI-1, with the 4G/4G genotype present in the study group and in controls (p = 1.00). NOS3 4a/4a was present in 4% of the study group and in none of the 100 controls (p = 0.123). In this study, we also discovered a new variant in the NOS3 gene which was named 4c allele and was encountered in 1 patient and in 1 control subject. Conclusion: There was no significant association between ACE I/D, PAI-1 4G/5G and NOS3 4a/4b and the occurrence of first-trimester RM. In-depth investigation of the association of NOS3 4a/4a with RM is strongly recommended.

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Angiotensin-converting enzyme insertion-deletion polymorphism in normotensive and pre-eclamptic pregnancies

Abstract: This study has found no evidence that the insertion-deletion polymorphism in the angiotensin-converting enzyme gene is associated with pre-eclampsia.

Cited by 50 publications

References 1 publication

Interaction between the polymorphisms of the renin–angiotensin system in preeclampsia

Interaction between the polymorphisms of the renin–angiotensin system in preeclampsia

Maternal-Fetal Flow, Negative Events, and Preeclampsia

Polymorphisms in <i>NOS3, ACE </i>and<i> PAI-1</i> Genes and Risk of Spontaneous Recurrent Miscarriage in the Gaza Strip

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