| ObjectivePreeclampsia(PE)is a common gestational disorder with significant maternal and fetal mortality and morbidity and unclear etiopathogenesis.A systematic review was carried out to investigate the relationship of maternal circulating interleukin-1 beta(IL-1β)and interferon gamma(IFNG)in PE and PE risk with their respective gene polymorphisms.Materials and MethodsA systematic review was carried out through literature search of the three electronic databases of Web of Science,Embase and Pubmed with specific keywords for studies published on IL-1βand IFNG in PE from 1990 to April 2018.Studies were included in compliance with our selection criteria,relevant data was extracted,analyzed,and their quality evaluated using the Newcastle-Ottawa Scale(NOS)standard.Statistical analysis:1.Meta-analysis of parametric data was performed using Review Manager 5.1 software(Cochrane Collaboration,Oxford,United Kingdom)and reported as standard mean deviation(SMD)with 95%confidence interval(C1)for continuous data and as odds ratio(OR)with 95%C1for dichotomous data.According to heterogeneity test results;fixed or random effects model was used for analysis.P value<0.05 was considered statistically significant.2.Non-parametric data was analyzed through scatter plots using Microsoft Excel software.3.Sensitivity analysis was carried out through one-factor-at-a-time method and publication bias was measured as funnel plots and through calculation of Rosenthal’s fail-safe number.Results:We included 24 studies investigating IL-1βincluding 19 studies reporting maternal circulating levels and 5 reporting gene polymorphisms at-511T/C and-31T/C.For IFNG analysis,we included 27 studies,amongst which 16 reported maternal circulating levels and 5investigated IFNG+874T/A gene polymorphism.1.IL-1βin PE(1)Meta-analysis of 12 studies with IL-1βyielded a statistically significant(P=0.008)difference for the overall test effect(Z)=2.63 with a pooled SMD of 0.40(95%CI:0.10,0.69,I~2:86%).Subgroup analysis of IL-1βlevels in late pregnancy in 7 studies with case control design(P=0.02,SMD:0.70,95%CI:0.13-1.26,I~2:86%);7 studies with blood serum(P=0.04,SMD:0.83,95%CI:0.12-1.54,I~2:89%);4 studies of combined mild and severe PE(Z=3.21,P=0.001,SMD:1.02,95%CI:0.40-1.64,I~2:86%);3 studies of severe PE(P=0.02,SMD:1.35,95%CI:0.19-2.52,I~2:88%)and 4 studies with ELISA assay(P=0.01,SMD:0.92,95%CI:0.21-1.63,I~2:86%)showed statistically significant results.(2)Non-parametric data analysis of 7 studies of IL-1βin PE showed increase of cytokine levels in PE patients as compared with normotensive controls.(3)Meta-analysis of IL-1β-511T/C TT genotype(P<0.05,OR:1.65,95%CI:1.29-2.11)and TC genotype(P=0.03,OR:0.78,95%CI:0.62-0.97)were statistically significant.Analysis of IL-1β-31T/C TC genotype(P<0.05,OR:0.64,95%CI:0.51-0.80)and CC genotype(P<0.05,OR:1.92,95%CI:1.51-2.44)proved to have statistical significance.Analysis of IL-1β-511T/C CC and IL-1β-31T/C TT genotypes was statistically insignificant(P>0.05).2.IFNG in PE(1)The overall test effect of 16 studies with IFNG in PE was statistically significant(P<0.01,Z=4.44,SMD:1.10,95%CI:0.62-1.59,I~2:96%).Maternal circulating IFNG levels in 13studies of late pregnancy was statistically significant(P<0.01,SMD:1.42,95%CI:0.72-2.12;I~2:96%).Subgroup analysis of late pregnancy IFNG levels in 10 studies with case control design(P<0.01,SMD:1.62,95%CI:0.83-2.42,I~2:95%);10 studies with serum(P<0.01,SMD:1.88,95%CI:1.02-2.74,I~2:96%);4 studies with combined mild and severe PE(Z=2.90,P=0.004,SMD:1.39,95%CI:0.45-2.33,I~2:94%);3 studies with severe PE(P=0.09,SMD:2.68,95%CI:0.46-4.90,I~2:94%)and 9 studies with ELISA assay(P<0.01,SMD:1.88,95%CI:1.00-2.75,I~2:97%)had statistical significance.(2)Non-parametric data analysis of IFNG included 6 articles in which serum and plasma levels reported conflicting results.(3)IFNG+874T/A AT genotype was associated with PE(P=0.03,OR:1.32,95%CI:1.03-1.69)while AA and TT genotypes were not(P>0.05).Conclusions:1.Our meta-analysis illustrates a possible association of higher maternal circulating IL-1βconcentrations with preeclampsia.Subgroup analysis of case control studies,serum,severe PE,and ELISA immunoassay should possible association of IL-1βwith PE.Scatter plot diagrams representing median show that IL-1βlevels in preeclamptic patients are higher than in normotensive pregnant women.2.IL-1βgene polymorphisms at–511T/C TT and at-31T/C CC genotypes were possible risk factors for PE.TC genotypes of both IL-1β-511T/C and IL-1β-31T/C gene polymorphisms were possible protective factors of PE.However the genetic disequilibrium of both polymorphisms suggests that presence of each polymorphism is required for possibility of one genotype alone being considered as risk factor or protective factor.3.Our meta-analysis illustrates a possible association of higher maternal circulating IFNG concentrations with preeclampsia.Subgroup analysis of case control studies,serum,severe PE and ELISA immunoassay should possible association of IL-1βwith PE.Scatter plot diagrams representing median show that IL-1βlevels in preeclamptic patients have conflicting results in normotensive pregnant women.4.IFNG gene polymorphism at+874T/A AT genotype is a possible risk factor for PE. |
PDF Full Text Request