Positive association of Apolipoprotein E4 polymorphism with recurrent pregnancy loss in Iranian patients

Abstract

Numerous lines of evidence implicate Apolipoprotein E (Apo E) in lipid metabolism during pregnancy. Hence, a role for its polymorphism has been envisaged in recurrent pregnancy loss (RPL) considering major structural and functional differences between different Apo E genotypes. A case control study of 81 women with two or more pregnancy losses that did not have any other known risk factors including anatomic anomalies of the reproductive system, infections, immunologic factors, hormonal imbalances, chromosomal abnormalities and environmental factors was carried out. The control group consisted of 81 women with at least two healthy children and no RPL in their reproductive history. DNA was extracted from the peripheral blood following written consent and Apo E genotyping was carried out by amplifying exon 4 of the gene and subjecting it to digestion by HhaI restriction enzyme. Genotyping was concluded by analyzing different fragment sizes produced, which resulted in finding significantly higher frequency of combined E3/E4 and E4/E4 genotypes in the patients (about 20%) compared to the normal controls (2.4%). The genotypes were confirmed by DNA sequencing. Allelic frequency for E4 was 13.5% in the patients and only 1% in the non-RPL group. Our findings confirm and are in line with a number of similar studies carried out on other populations. Therefore, Apo E4 polymorphism seems to be contributing to the thrombophilic risk factors as a background to RPL.