Polo-like kinase 4 and Stromal antigen 3 are not associated with recurrent pregnancy loss caused by embryonic aneuploidy

Abstract

No genetic association with recurrent pregnancy loss (RPL) caused by embryonic aneuploidy has been found. Recent studies have indicated that the common genetic variant rs2305957, surrounding the PLK4 gene, contributes to mitotic-origin aneuploidy risk during human early embryo development. The decrease in meiosis-specific cohesin causes predivision of sister chromatids in the centromere and chromosome segregation errors. STAG3 is a component of cohesin and is a meiosis-specific gene. Our case-control study included 184 patients with RPL whose previous products of conception (POC) exhibited aneuploidy and 190 fertile control women without a history of miscarriage. We performed a genetic association study to examine the genotype distribution at PLK4 (rs2305957) and STAG3 in patients with RPL caused by aneuploidy compared with controls. Regarding STAG3, SNPs with a minor allele frequency (MAF) threshold > 0.05 that were predicted to be binding sites of transcription factors and that showed significant associations in expression quantitative trait locus (e-QTL) analysis were selected. No significant differences in the MAF or distribution in any model of PLK4 (rs2305957) and 5 selected tag SNPs in STAG3 were found between the patients and controls. A further genome-wide association study is needed since a combination of genetic risk alleles might be useful in predicting future age-dependent RPL caused by aneuploidy.

Pregnancy: Finding genes to predict recurrent pregnancy loss

Researchers have ruled out two potential genetic causes of recurrent pregnancy loss (RPL). Defined as loss of two or more pregnancies at any stage, RPL is caused by loss or gain of a chromosome (aneuploidy) in almost half of cases. Identifying genetic factors could help to predict the risk of RPL, which increases with maternal age. Hiroyuki Yoshihara at Nagoya City University in Japan and co-workers investigated whether two genes involved in chromosome distribution during cell division were associated with aneuploidy-related RPL. In a study of almost 400 women, half of whom had experienced RPL, they showed that neither gene was involved. Because multiple genetic factors could combine to cause RPL, the researchers recommend a genome-wide search. A better understanding of the genetic risk factors of RPL could help women in making fertility-related choices.