scholarly journals Three polymorphisms of renin-angiotensin system and preeclampsia risk

2020 ◽  
Vol 37 (12) ◽  
pp. 3121-3142
Author(s):  
Chen Wang ◽  
Xiao Zhou ◽  
Huai Liu ◽  
Shuhui Huang

Abstract Purpose 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.

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1600
Author(s):  
Hady Mohammadi ◽  
Mehrnoush Momeni Roochi ◽  
Masoud Sadeghi ◽  
Ata Garajei ◽  
Hosein Heidar ◽  
...  

Background and objective: Interleukins (ILs), as important biochemical mediators, control the host response to inflammation and are associated with bone resorption. In the present meta-analysis, we investigated the association between IL−1 polymorphisms and susceptibility to dental peri-implant disease (PID). Materials and methods: We searched Web of Science, Cochrane Library, Scopus, and PubMed/Medline databases for studies published until 9 September2021, without any restrictions. We calculated the crude OR and 95% confidence intervals (CI) to estimate the associations between IL−1 polymorphisms and PID risk in the five genetic models. We further performed the subgroup analysis, sensitivity analysis, meta-regression, trial sequential analysis, and calculated the publication bias. Results: Out of 212 retrieved records, sixteen articles were used in the meta-analysis. There was no association between IL−1A (–889), IL−1B (−511), IL−1B (+3953), and IL−1RN (VNTR) polymorphisms and the risk of dental PIDs, but there was an increased risk of IL−1B (+3954) in the patients with PIDs. In addition, an association of the composite genotype of IL−1A (−889)/IL−1B (+3953) was observed with the risk of PIDs, but not for the composite genotype of IL−1A (−889)/IL−1B (+3954). The publication year, the ethnicity, sample size, and the outcome were significantly influenced pooled estimates of some genetic models. Trial sequential analysis showed the lack of sufficient sample sizes in the studies. Conclusions: Among IL−1 polymorphisms evaluated in the meta-analysis, the composite genotype of IL−1A (−889)/IL−1B (+3953) and IL−1B (+3954) were the only polymorphisms associated with the risk of PID. The T allele and CT genotype of IL−1B (+3954) polymorphism were also associated with an elevated risk of PID.


Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-215322
Author(s):  
Hyun Woo Lee ◽  
Chang-Hwan Yoon ◽  
Eun Jin Jang ◽  
Chang-Hoon Lee

BackgroundThe association of ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) with disease severity of patients with COVID-19 is still unclear. We conducted a systematic review and meta-analysis to investigate if ACEI/ARB use is associated with the risk of mortality and severe disease in patients with COVID-19.MethodsWe searched all available clinical studies that included patients with confirmed COVID-19 who could be classified into an ACEI/ARB group and a non-ACEI/ARB group up until 4 May 2020. A meta-analysis was performed, and primary outcomes were all-cause mortality and severe disease.ResultsACEI/ARB use did not increase the risk of all-cause mortality both in meta-analysis for 11 studies with 12 601 patients reporting ORs (OR=0.52 (95% CI=0.37 to 0.72), moderate certainty of evidence) and in 2 studies with 8577 patients presenting HRs. For 12 848 patients in 13 studies, ACEI/ARB use was not related to an increased risk of severe disease in COVID-19 (OR=0.68 (95% CI=0.44 to 1.07); I2=95%, low certainty of evidence).ConclusionsACEI/ARB therapy was not associated with increased risk of all-cause mortality or severe manifestations in patients with COVID-19. ACEI/ARB therapy can be continued without concern of drug-related worsening in patients with COVID-19.


2021 ◽  
Vol 9 ◽  
Author(s):  
Daojing Ying ◽  
Mengjie Jiang ◽  
Liping Rong ◽  
Hongjie Zhuang ◽  
Lizhi Chen ◽  
...  

Background: Studies have identified that MIF -173 G>C gene polymorphism is associated with idiopathic nephrotic syndrome (INS) susceptibility and steroid resistance, but the results remain inconclusive.Methods: We searched PubMed, Embase, and Web of Science for relevant studies published before 31 March 2021. Pooled data were reported as odds ratio (OR) with 95% confidence interval (CI). Noteworthiness of significant OR was estimated by the false positive report probability (FPRP) test. Trial sequential analysis (TSA) was used to control type I and type II errors.Results: We selected seven case-control studies that included 1,026 INS children (362 were steroid-resistant NS and 564 were steroid-sensitive NS) and 870 controls. The results showed that MIF -173 G>C polymorphism was significantly associated with INS susceptibility in allelic, heterozygous and dominant genetic models (C vs. G: OR = 1.325, 95% CI: 1.011-1.738; GC vs. GG: OR = 1.540, 95% CI: 1.249-1.899; CC + GC vs. GG: OR = 1.507, 95% CI: 1.231-1.845), and FPRP test and TSA indicated that the associations were true in heterozygous and dominant models. The pooled results also revealed that MIF -173 G>C polymorphism was significantly associated with steroid resistance in allelic, homozygous and recessive models (C vs. G: OR = 1.707, 95% CI: 1.013-2.876; CC vs. GG: OR = 4.789, 95% CI: 2.109-10.877; CC vs. GC + GG: OR = 4.188, 95% CI: 1.831-9.578), but FPRP test indicated that all these associations were not noteworthy. Furthermore, TSA revealed that the non-significant associations between MIF -173 G>C polymorphism and steroid resistance in heterozygous and dominant models were potential false negative.Conclusions: This meta-analysis could draw a firm conclusion that MIF -173 G>C polymorphism was significantly associated with increased INS risk in heterozygous and dominant genetic models. MIF -173 G>C polymorphism was not likely to affect steroid responsiveness, but more studies were needed to confirm.


2020 ◽  
Vol 40 (7) ◽  
Author(s):  
Jing Liu ◽  
Guang Song ◽  
Ge Zhao ◽  
Tao Meng

Abstract Background: It is well known that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) rs4402960 polymorphism is associated with Type 2 diabetes mellitus, which has a shared genetic background with gestational diabetes mellitus (GDM). Previous studies have yielded controversial results about the link between IGF2BP2 rs4402960 polymorphism and GDM risk. Thus, a meta-analysis was performed to obtain more conclusive results. Methods: Clinical and genotype data were determined for 305 GDM and 1216 healthy participants recruited. Eligible studies were retrieved in PubMed, Web of science, EMBASE, and Scopus. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to evaluate the relationship between IGF2BP2 polymorphisms and GDM susceptibility in five genetic models. The subgroup stratified analysis and trial sequential analysis (TSA) were performed. Results: In this case–control study, no significant association was revealed between IGF2BP2 polymorphism and GDM (P>0.05). When combined with the previous studies in the meta-analysis, there was no statistical association between IGF2BP2 polymorphism and GDM (allele model: OR = 1.01, 95% CI = 0.86–1.18; dominant model: OR = 1.00, 95% CI = 0.81–1.24; recessive model: OR = 1.08, 95% CI = 0.91–1.29; heterozygous model: OR = 0.99, 95% CI = 0.80–1.24; homozygous model: OR = 1.06, 95% CI = 0.78–1.42). No association was observed in five genetic models in each subgroup. TSA indicated sufficient proof of such null association in the overall population. Conclusions: This meta-analysis provides sufficient statistical evidence indicating null association between IGF2BP2 rs4402960 polymorphism and GDM risk.


2021 ◽  
Vol 14 (8) ◽  
pp. 824
Author(s):  
Joo-Hee Kim ◽  
Jeong Yee ◽  
Byung-Chul Chang ◽  
Hye-Sun Gwak

Background: This study aimed to investigate the effects of genetic variants and haplotypes in the renin–angiotensin system (RAS) on the risk of warfarin-induced bleeding complications at therapeutic international normalized ratios (INRs). Methods: Four single nucleotide polymorphisms (SNPs) of AGT, two SNPs of REN, three SNPs of ACE, four SNPs of AGTR1, and one SNP of AGTR2, in addition to VKORC1 and CYP2C9 variants, were investigated. We utilized logistic regression and several machine learning methods for bleeding prediction. Results: The study included 142 patients, among whom 21 experienced bleeding complications. We identified a haplotype, H2 (TCG), carrying three SNPs of ACE (rs1800764, rs4341, and rs4353), which showed a significant relation with bleeding complications. After adjusting covariates, patients with H2/H2 experienced a 0.12-fold (95% CI 0.02–0.99) higher risk of bleeding complications than the others. In addition, G allele carriers of AGT rs5050 and A allele carriers of AGTR1 rs2640543 had 5.0- (95% CI 1.8–14.1) and 3.2-fold (95% CI 1.1–8.9) increased risk of bleeding complications compared with the TT genotype and GG genotype carriers, respectively. The AUROC values (mean, 95% CI) across 10 random iterations using five-fold cross-validated multivariate logistic regression, elastic net, random forest, support vector machine (SVM)–linear kernel, and SVM–radial kernel models were 0.732 (0.694–0.771), 0.741 (0.612–0.870), 0.723 (0.589–0.857), 0.673 (0.517–0.828), and 0.680 (0.528–0.832), respectively. The highest quartile group (≥75th percentile) of weighted risk score had approximately 12.0 times (95% CI 3.1–46.7) increased risk of bleeding, compared to the 25–75th percentile group, respectively. Conclusion: This study demonstrated that RAS-related polymorphisms, including the H2 haplotype of the ACE gene, could affect bleeding complications during warfarin treatment for patients with mechanical heart valves. Our results could be used to develop individually tailored intervention strategies to prevent warfarin-induced bleeding.


2017 ◽  
Vol 32 (3) ◽  
pp. 297-304 ◽  
Author(s):  
Zicheng Xu ◽  
Xiao Li ◽  
Zhiqiang Qin ◽  
Jianxin Xue ◽  
Jingyuan Wang ◽  
...  

Background Individual studies of the association between N-acetyltransferase 1 (NAT1)*10 allele and bladder cancer susceptibility have shown inconclusive results. To derive a more precise estimation of any such relationship, we performed this systemic review and updated meta-analysis based on 17 publications. Methods A total of 17 studies were investigated with 4,322 bladder cancer cases and 4,944 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. Subgroup analyses were conducted based on ethnicity, sex, source of controls and detecting methods. Then trial sequential analysis was performed to evaluate whether the evidence of the results was sufficient and reduce the risk of type I error. Results There was no association between NAT1*10 allele and bladder cancer risk in a random-effects model (OR = 0.96, 95% CI, 0.84-1.10) or in a fixed-effects model (OR = 0.95, 95% CI, 0.87-1.03). In addition, no significantly increased risk of bladder cancer was found in any other subgroup analysis. Then, trial sequential analyses demonstrated that the results of our study need to be further verified. Conclusions Despite its limitations, the results of the present meta-analysis suggested that there was no association between NAT1* 10 allele and bladder cancer risk. More importantly, our findings need to be further validated regarding whether being without the NAT1*10 allele could in the future be shown to be a potential marker for the risk of bladder cancer.


2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Lorenzo Ball ◽  
◽  
Ary Serpa Neto ◽  
Valeria Trifiletti ◽  
Maura Mandelli ◽  
...  

Abstract Purpose In patients with acute respiratory distress syndrome (ARDS), lung recruitment could be maximised with the use of recruitment manoeuvres (RM) or applying a positive end-expiratory pressure (PEEP) higher than what is necessary to maintain minimal adequate oxygenation. We aimed to determine whether ventilation strategies using higher PEEP and/or RMs could decrease mortality in patients with ARDS. Methods We searched MEDLINE, EMBASE and CENTRAL from 1996 to December 2019, included randomized controlled trials comparing ventilation with higher PEEP and/or RMs to strategies with lower PEEP and no RMs in patients with ARDS. We computed pooled estimates with a DerSimonian-Laird mixed-effects model, assessing mortality and incidence of barotrauma, population characteristics, physiologic variables and ventilator settings. We performed a trial sequential analysis (TSA) and a meta-regression. Results Excluding two studies that used tidal volume (VT) reduction as co-intervention, we included 3870 patients from 10 trials using higher PEEP alone (n = 3), combined with RMs (n = 6) or RMs alone (n = 1). We did not observe differences in mortality (relative risk, RR 0.96, 95% confidence interval, CI [0.84–1.09], p = 0.50) nor in incidence of barotrauma (RR 1.22, 95% CI [0.93–1.61], p = 0.16). In the meta-regression, the PEEP difference between intervention and control group at day 1 and the use of RMs were not associated with increased risk of barotrauma. The TSA reached the required information size for mortality (n = 2928), and the z-line surpassed the futility boundary. Conclusions At low VT, the routine use of higher PEEP and/or RMs did not reduce mortality in unselected patients with ARDS. Trial registration PROSPERO CRD42017082035.


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