title: Insertion/deletion polymorphism in intron 16 of ACE gene in idiopathic recurrent spontaneous abortion: case-control study, systematic review and meta-analysis.
abstract: The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin I-converting enzyme gene (ACE) has been extensively studied as a predisposing factor for idiopathic recurrent spontaneous abortion (IRSA). A case-control study including 149 women with ≥3 spontaneous abortions and 149 controls was performed to test the association of ACE I/D polymorphism with IRSA. A systematic review was conducted of previous case-control studies, with strict selection criteria for meta-analyses. We also aimed to evaluate the potential differences in summary estimates between studies defining IRSA as ≥2 and ≥3 spontaneous abortions. Genotyping was performed by PCR, and systematic review conducted using PubMed and Scopus. There was no association of the polymorphism with IRSA in Slovenian women. Sixteen case-control studies, showing substantial differences regarding IRSA definition and selection criteria for women were identified. Meta-analysis was performed and included four studies defining IRSA as ≥2 spontaneous abortions and the current study, which defined IRSA as ≥3 spontaneous abortions. Based on random effects model, meta-analysis conducted on 1192 patients and 736 controls showed no association with IRSA under dominant(DD+IDvsII) and recessive(DDvsID+II) genetic models. Well-designed studies are needed to evaluate the role of ACE I/D polymorphism in IRSA defined as ≥3 spontaneous abortions.
authors.affiliation: Department of biology and medical genetics, Faculty of medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia. Electronic address: nina.pereza@medri.uniri.hr.
authors.forename: Nina
authors.initials: N
authors.lastname: Pereza
authors.affiliation: Department of biology and medical genetics, Faculty of medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Saša
authors.initials: S
authors.lastname: Ostojić
authors.affiliation: Department of biology and medical genetics, Faculty of medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Matea
authors.initials: M
authors.lastname: Zdravčević
authors.affiliation: Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Marija
authors.initials: M
authors.lastname: Volk
authors.affiliation: Department of biology and medical genetics, Faculty of medicine, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Miljenko
authors.initials: M
authors.lastname: Kapović
authors.affiliation: Clinical Institute of Medical Genetics, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.
authors.forename: Borut
authors.initials: B
authors.lastname: Peterlin
mesh_terms: D000026:Abortion, Habitual / Q000235:genetics*; D000483:Alleles; D016022:Case-Control Studies; D019317:Evidence-Based Medicine; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D054643:INDEL Mutation; D007438:Introns; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D011247:Pregnancy; D017524:Slovenia
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: angiotensin I-converting enzyme; evidence-based medicine; genetic variability; insertion/deletion polymorphism; pregnancy; recurrent spontaneous abortion