ACE gene rs4343 polymorphism elevates the risk of preeclampsia in pregnant women (original) (raw)
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Journal of the Renin-Angiotensin-Aldosterone System, 2014
Introduction: Several studies have assessed the relationship between blood pressure (BP) and polymorphisms within the genes encoding angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and angiotensin-converting enzyme (ACE). However, considering the relatively large discrepancy in frequency and impact of these variants between ethnic groups and populations, still unavailable data from Algerian population are needed. Objective: Our purpose is to evaluate the association between the AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms and variations in systolic (SBP), diastolic (DBP) and pulse pressure (PP) values. Methods: The associations with BP were assessed in a representative sample of 115 male subjects free of coronary heart disease (CHD). The AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms were determined by PCR-ASO and PCR-RFLP analysis, respectively. Results: We showed no associations between the AGT M235T, AT1R +1166A/C nor the ACE I/D polymorphisms with variations in BP values. However, concerning the ACE I/D polymorphism, subjects carrying the ACE I allele tended to have higher SBP (+4.1 mmHg) and PP values (+3.2 mmHg) than DD subjects (adjusted p = 0.087 and p = 0.102, respectively). Conclusion: The ACE I/D polymorphism needs further investigation in a larger Algerian study, especially concerning its putative impact on SBP and PP.
Gene, 2014
The possible association of angiotensin type 2 receptor (AT2R) -1332 G:A polymorphism with susceptibility to preeclampsia was studied in 252 women consisted of 155 women with preeclampsia and 97 healthy pregnant women. Also, the interaction of this polymorphism with angiotensin type 1 receptor (AT1R) 1166 A:C, angiotensin converting enzyme insertion/deletion (ACE I/D) and also with matrix metalloproteinase-9 (MMP-9) -1562 C:T polymorphism was investigated. The AT2R -1332 G:A polymorphism was detected using PCR-RFLP method. Significantly higher frequencies of GG+GA genotype and G allele of AT2R were observed in mild (80.2%, p=0.003 and 47.5%, p=0.012, respectively) and severe (77.8%, p=0.034 and 48.1%, p=0.026, respectively) preeclampsia compared to controls (60.8% and 35.1%, respectively). The presence of G allele was associated with 1.69-fold increased risk of preeclampsia (p=0.005). In severe preeclamptic women, systolic and diastolic blood pressures in the presence of GG+GA genot...
Angiotensin-Converting Enzyme I/D polymorphism and preeclampsia risk: Evidence of small-study bias
PLoS Medicine, 2006
Background: Inappropriate activation of the renin–angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks. Methods and Findings: A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR 0.95 [95% CI, 0.81–1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR 0.90 [95% CI, 0.77–1.06]) and using other genetic models of inheritance. A metaanalysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07–1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased. Conclusions: It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of adequate size.
European Journal of Obstetrics & Gynecology and Reproductive Biology, 2017
To investigate the association of the gene polymorphisms of: angiotensinogen (AGT), renin (REN), angiotensin II receptor 1 (AT1R) and angiotensin II receptor 2 (AT2R), in the pathogenesis of PE in South African Black women. Methodology (Study design) 603 pregnant women; 246 normotensive and 357 with PE (early-onset=187, late-onset=170), were recruited. Each study group was subdivided into HIV infected and uninfected groups. The distribution and frequencies of gene polymorphisms of AGT (M235T), REN (C-5312T), AT1R (A1166C) and AT2R (C3123A) were determined in purified DNA by Real Time Polymerase Chain Reaction. Results The distribution of T allele and TT genotype of AGT in PE were significantly higher than the normotensive group (95% vs 91%, OR 1.9, 95%CI 1.2-3.1, p=0.0051; 90% vs 83%, OR 1.84, 95%CI 2 1.11-3.05, p= 0.01) respectively. The distributions of genotypes of REN, AT1R and AT2R were similar in PE and normotensive groups. Conclusion The T allele of AGT may play a role in the pathogenesis of PE. The genotypes of REN, AT1R and AT2R were not associated with the development of PE.
2005
ABSTRACT The present prospective long-term study was conducted to evaluate whether the DD genotype could also be associated with a higher prevalence of hypertension in healthy subjects over 6 years of follow-up. We also investigated the effects of the ACE-I/D genotypes on diastolic function by echocardiographic method in healthy subjects without any risk factors and without any events after 6 years of follow-up. 684 healthy volunteers (aged 25–55 years) with acceptable echocardio-graphic window were enrolled. Physical examination,12-lead ECG, echocardiograms and venous blood samples for DNA analysis were performed. All subjects had a clinical evaluation each year for the 6 year. In addition,275 subjects without any risk factors underwent an ECHO every year of the follow-up, to check the influence of genotypes on myocardial diastolic performances. All 684 subjects completed 6 years of follow up. We obtained 3 genetically distinct groups. ACE-DD group,(n=225,80F/145M,mean age 43.4±7.6 years),had 42 hypertensive subjects (18.3%), 5 heart failure (HF) subjects and 6 subjects with acute coronary syndromes (ACS).There was not association between family history,smoking habit,hypercholesterolemia and events.ACE-ID group: (n=335, 116F/219M, mean age 43.6±7 years),had 16 hypertensive subjects (4.7%),and 3 subjects with ACS. ACE-II group:(n=124,45/79 F/M, mean age 42.5±6.9 years),had 2 hypertensive subjects (1.6%), and 1 HF subject. The incidence of hypertension and cardiovascular events, were significantly higher in ACE-DD (53 cases, 23%) than ACE-ID and ACE-II groups (20 and 3 cases,5.9% and 2.4%, respectively), p=0.0001. The higher incidence of hypertension was observed in the older age groups (36–45 and 46–55 years) with ACE-DD and ACE-ID genotypes. Moreover, ACE-DD significantly and early affected myocardial diastolic properties in the whole examined group, also when stratified for the age. There was a reduction of E/A ratio and it was more evident in subjects aged 36–45 and 46–55 years, p=0.0001.Our data suggest that ACE-DD polymorphism is associated to a higher incidence of hypertension and appears to affect the diastolic function.
The American Journal of Human Genetics, 2001
Considerable effort has been expended to determine whether the gene for angiotensin I-converting enzyme (ACE) confers susceptibility to cardiovascular disease. In this study, we genotyped 13 polymorphisms in the ACE gene in 1,343 Nigerians from 332 families. To localize the genetic effect, we first performed linkage and association analysis of all the markers with ACE concentration. In multipoint variance-component analysis, this region was strongly linked to ACE concentration (maximum LOD score 7.5). Likewise, most of the polymorphisms in the ACE gene were significantly associated with ACE ( ). The two most highly associated polymorphisms, P ! .0013 ACE4 and ACE8, accounted for 6% and 19% of the variance in ACE, respectively. A two-locus additive model with an additive # additive interaction of these polymorphisms explained most of the ACE variation associated with this region. We next analyzed the relationship between these two polymorphisms (ACE4 and ACE8) and blood pressure (BP). Although no evidence of linkage was detected, significant association was found for both systolic and diastolic BP when a two-locus additive model developed for ACE concentration was used. Further analyses demonstrated that an epistasis model provided the best fit to the BP variation. In conclusion, we found that the two polymorphisms explaining the greatest variation in ACE concentration are significantly associated with BP, through interaction, in this African population sample. Our study also demonstrates that greater statistical power can be anticipated with association analysis versus linkage, when markers in strong linkage disequilibrium with a trait locus have been identified. Furthermore, alllelic interaction may play an important role in the dissection of complex traits such as BP.
International Journal of Biomedicine, 2023
The aim of our study was to investigate the relationship between the ACE I/D and PAI-1 4G/5G polymorphisms and recurrent pregnancy loss (RPL) in Sudanese women. Methods and Results: A total of 232 people participated in this case-control study, including 119 women who had been diagnosed with RPL (Case group) and 113 healthy women (Control group). The case group (RPL) consisted of Sudanese women (mean age of 31.3+5.9 years) who had at least three unfavorable pregnancy outcomes. Women in the control group (Control) were matched by age (mean age of 30.3+5.4 years), had at least two healthy pregnancies, and had no history of unfavorable pregnancy outcomes or recurrent losses. Genomic DNA samples were isolated from the whole blood by using the GF-1 Blood DNA Extraction Kit (Vivantis Technologies Sdn. Bhd., Malaysia). The status of the PAI-1 4G/5G and ACE I/D polymorphism was determined by PCR. Analysis of the multiplicative and additive models for the ACE I/D polymorphism showed a significant risk of RPL with the carriage of the D allele (OR=2.07, 95% CI: 1.28-3.35, P=0.003) and the homozygous DD genotype (OR=2.40, 95% CI: 1.34-4.29, P=0.008). The multiplicative and additive models for the PAI-1 4G/5G polymorphism showed a significant risk of RPL with the carriage of the 4G allele (OR=3.11, 95% CI: 2.12-4.58, P=0.000) and the homozygous 4G/4G genotype (OR=3.09, 95% CI: 1.77-5.39, P=0.000). However, the carriage of risk-polymorphic markers, the ACE I/D and PAI-1 4G/5G polymorphisms, was not associated with the number of RPL. The combined carriage of the homozygous DD genotype and heterozygous ID genotype of the ACE I/D polymorphism with the homozygous 4G/4G genotype of the PAI-1 4G/5G polymorphism occurs significantly more often in RPL women than healthy women (P=0.000 and P=0.019, respectively). Carriage of the PAI-1 5G/5G genotype in healthy women was not associated with the ACE I/D polymorphism. Conclusion: Testing for the ACE I/D and PAI-1 4G/5G polymorphisms should be part of the standard examination for patients with RPL.
BMC Research Notes, 2012
Background: Leptin is known to be elevated in pre-eclampsia/ pregnancy induced hypertension (PE/PIH). However the reports on the association of leptin receptor (LEPR) c.668A>G polymorphism with PE/PIH are inconsistent. Findings: LEPR c.668A>G polymorphism was studied in a cohort of women with PE/PIH (N = 61) and normotensive pregnancies (N = 40) by polymerase chain reaction / restriction fragment length polymorphism. Genotype and allele frequencies were in Hardy-Weinberg equilibrium within both groups (Chi square test). Allele and genotype frequencies were not significantly different between PE/PIH and normotensive pregnancies (Chi square test). Leptin levels (Kruskal Wallis analysis of variance) and leptin/body mass index (one way analysis of variance) were not significantly different between genotypes within each group. However, leptin (Mann Whitney U test) and leptin normalised to body mass index (unpaired t test) were significantly higher in PE/PIH women homozygous and heterozygous for the G668 allele than in respective normotensives. Conclusions: Whether the leptin receptor c.668A>G polymorphism increases the risk of developing PE/PIH in Sri Lankan women remains inconclusive in view of the smaller sample studied. However leptin levels in PE/PIH appeared to be modulated by this polymorphism.