The aetiological mechanism of preeclampsia (PE) is unclear exactly, so we attempted to investigate the association between susceptibility to preeclampsia and renin-angiotensin-aldosterone system (RAAS) gene polymorphisms to explore the aetiology in terms of genetics. A systematic search was performed in electronic databases to identify relevant studies. Eventually 73 studies were enrolled, odds ratios were generated by 5 genetic models. In overall analysis, significant associations were detected for AGT M235T, AT1R A1166C and CYP11B2 C344T whereas negative correlation was shown for AGT T174M. As stratified by race and geography, AGT 235T allele and AT1R 1166C allele increased preeclampsia risk and AGT T174M was justified uncorrelated with preeclampsia. Our meta-analysis illustrated that AGT 235T allele and AT1R 1166C allele increased and CYP11B2 344T allele decreased preeclampsia risk while AGT T174M polymorphism did not change preeclampsia risk. Hence, pregnant women carrying high-risk genotypes need strengthened management to prevent and early identification of preeclampsia.

OBJECTIVE: Some data suggest an association between the single nucleotide polymorphisms AGT T704C, ACE I/D, and AT1R A1166C and preeclampsia, but overall, the data are conflicting; the aim of our study was to discover a more stable and reliable association between these polymorphisms and PE risk.
METHODS: A comprehensive literature search for this meta-analysis was conducted. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated to evaluate the strength, and heterogeneity test was conducted. Trial sequential analysis was also performed.
RESULTS: A total of forty studies were finally included in our meta-analysis. The AGT T704C polymorphism was associated with PE risk in three genetic models (dominant OR = 1.33, 95%CI = 1.12-1.59; heterozygote OR = 1.26, 95%CI = 1.05-1.52; homozygote OR = 1.44, 95%CI = 1.14-1.83). No heterogeneity was observed in the three genetic models for the ACE I/D polymorphism. For subgroup analysis by geography, no significant association was detected. Significant associations were observed in mixed race, early-onset, late-onset, and more than 200 subgroups for the AT1R A1166C polymorphism; however, only one study was analyzed in these subgroups.
CONCLUSIONS: Our results indicated the AGT T704C and ACE I/D polymorphisms were associated with an increased risk of PE. Increased risks were also observed for the two polymorphisms in subgroups including Asians, Europeans, Caucasoid, and Mongoloid. Moreover, an increased PE risk with the ACE I/D polymorphism in the severe PE population was also detected. Regarding the AT1R A1166C polymorphism, weak associations were observed, but further studies are required.

BACKGROUND: There are very limited data for Iranian populations on the predisposing genetic factors for acute coronary syndrome (ACS).
OBJECTIVE: The objective of the present study was to investigate the association of the angiotensin II type 1 receptor (AT1R) gene polymorphism and ACS in an Iranian population.
METHODS: This cross-sectional study was conducted among 263 subjects (97 men and 166 women). Patients (n = 128) aged 30 - 80 years with chest pain were recruited from the emergency department of Ghaem Hospital (Mashhad, Iran). A 12-lead electrocardiograph plus creatine kinase MB (CK-MB) levels were used as the basis for the diagnosis of myocardial ischemia. The control group was selected from age-matched healthy subjects (n = 135). Non-enzymatic kits were used for extraction of DNA from blood samples. Polymerase chain reaction (PCR) was performed to amplify the DNA fragments. For restriction fragment length polymorphism (RFLP) determination, the DdeI enzyme was used to digest the amplified DNA fragments. Statistical analyses were performed using SPSS version 13.0.
RESULTS: There was no statistical difference in the genotype frequency of patients and healthy subjects with regard to age and gender (P > 0.05).
CONCLUSIONS: The AT1R A1166C polymorphism appeared not to be associated with the presence of ACS in the population studied.

BACKGROUND: The renin-angiotensin system (RAS) has been considered to play an important role in the regulation of blood pressure. This study aimed to investigate the correlation between RAS gene polymorphisms and essential hypertension (EH) in the Chinese Yi ethnic group.
METHODS: A total of 244 EH subjects and 185 normotensive individuals from the Chinese Yi ethnic group were genotyped for AGT M235T (rs699), AT1R A1166C (rs5186), ACE I/D (rs4340) and ACE G2350A (rs4343) polymorphisms by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method.
RESULTS: Significant differences in the allele and genotype frequency of ACE G2350A were observed between the EH cases and controls (p=0.001, 0.002). After being grouped by gender, significant differences in the allele and genotype frequency of ACE G2350A and AT1R A1166C were observed between females of the EH cases and controls (ACE G2350A: p=0.000, 0.002; AT1R A1166C: p=0.008, 0.011). After excluding the influence of multifactorial interactions, the ACE G2350A polymorphism is significantly associated with the pathogenesis of EH in the Chinese Yi ethnic group (odds ratio (OR)=1.656, 95% confidence interval (CI) 1.807-2.524, p=0.019).
CONCLUSIONS: The RAS-related ACE G2350A polymorphism is associated with the pathogenesis of EH in the Chinese Yi ethnic group.

BACKGROUND: Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN).
METHODS: The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699).
RESULTS: During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction).
CONCLUSIONS: ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did.

BACKGROUND: The aim of the present study was to investigate the association between angiotensin converting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type-1 receptor (AT1R) A1166C polymorphisms with the risk of preeclampsia and lipid peroxidation in preeclamptic women from Western Iran.
METHODS: One hundred and ninety-eight preeclamptic women (128 women with mild and 70 with severe forms) and 100 age- and parity-matched controls were enrolled in this case-control study.
RESULTS: The presence of D allele of ACE was associated with a 1.8-fold increased risk of preeclampsia (p=0.002) in total preeclamptic patients. The frequency of AT1R AC+CC genotypes was higher in mild preeclamptic women (32%) compared to controls (27.2%) (p>0.05). In mild preeclamptic women with ID genotype, the level of total antioxidant capacity (TAC) was significantly decreased compared to those with II genotype. Also, there was a trend toward increasing malondialdehyde (MDA) and decreasing TAC levels in mild and severe preeclamptic women with AT1R AA through CC genotypes.
CONCLUSIONS: Our study indicates that lipid peroxidation and oxidative stress are involved in the development of preeclampsia that might be influenced by polymorphism in the renin-angiotensin-aldosterone system genes.