Insertion/deletion polymorphism in intron 16 of ACE gene in idiopathic recurrent spontaneous abortion: case-control study, systematic review and meta-analysis

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.