title: Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: a systematic review and meta-analysis.
abstract: BACKGROUND
  Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of recurrent miscarriage, but the impact is unclear due to inconsistencies among those studies. This study aimed to quantify the strength of the association between ACE I/D polymorphism and recurrent miscarriage risk by performing a systematic review and meta-analysis.
  
  
  METHODS
  We searched PubMed, Embase, Web of Science, and Wanfang Medicine databases for eligible articles relating the association between ACE I/D polymorphism and risk of recurrent miscarriage in humans. We estimated the summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association.
  
  
  RESULTS
  Eleven studies with a total of 3357 individuals were included in this meta-analysis. Compared to the ACE II genotype, DD and ID were both associated with increased risk of recurrent miscarriage (OR DD versus II=1.81, 95% CI 1.23-2.66, P=0.003; OR ID versus II=1.50, 95% CI 1.25-1.80, P<0.001). Sensitivity analyses further confirmed the association above. No evidence of publication bias was observed.
  
  
  CONCLUSIONS
  Meta-analyses of available data show a significant association between ACE I/D polymorphism and recurrent miscarriage risk, and the ACE polymorphic D allele contributes to increased risk of recurrent miscarriage.
authors.affiliation: Department of Obstetrics, Maternal and Child Health Hospital of Weifang, Weifang 261011, China.
authors.forename: Zengfang
authors.initials: Z
authors.lastname: Wang
authors.forename: Pingping
authors.initials: P
authors.lastname: Wang
authors.forename: Ximei
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: He
authors.forename: Zengyan
authors.initials: Z
authors.lastname: Wang
authors.forename: Donghua
authors.initials: D
authors.lastname: Xu
authors.forename: Jiying
authors.initials: J
authors.lastname: Hu
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020022:Genetic Predisposition to Disease; D006801:Humans; D016254:Mutagenesis, Insertional; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011247:Pregnancy; D017594:Publication Bias; D012306:Risk
chemical_list: D007703:Peptidyl-Dipeptidase A
keywords: 95% CI; 95% confidence interval; ACE; ACE I/D; Angiotensin-converting enzyme; Gene polymorphism; HWE; Hardy–Weinberg equilibrium; Meta-analysis; OR; Recurrent miscarriage; odds ratio; skewed X chromosome inactivation.; skewed XCI