Maternal and Fetal SERPINA3 Polymorphisms and Risk of Preeclampsia: A Dyad and Triad Based Case-Control Study

Area of Science:

• Genetics
• Obstetrics
• Reproductive Medicine

Background:

• Serine protease inhibitor A3 (SERPINA3) is implicated in placental dysfunction.
• Hypertensive disorders of pregnancy (HDPs), including severe preeclampsia (sPE) and HELLP syndrome, are significant maternal health concerns.

Purpose of the Study:

• To investigate the association between SERPINA3 gene polymorphisms and haplotypes with HDPs and sPE/HELLP syndrome.
• To explore parent-of-origin effects in the context of these pregnancy complications.

Main Methods:

• Retrospective case-control study involving two cohorts: HDP mother-baby dyads and sPE/HELLP mother-father-baby triads.
• Genotyping of two SERPINA3 SNPs (rs4934 and rs1884082) from DNA samples.
• Genetic association analyses using the Haplin package in R.

Main Results:

• No significant association was found between individual SERPINA3 SNPs or haplotypes and the risk of HDPs or sPE/HELLP.
• Significant parent-of-origin effects were observed: maternally inherited alleles of rs4934 decreased risk, while paternally inherited alleles increased risk.
• Maternal carriage of double copies of both SNPs was associated with increased risk.

Conclusions:

• SERPINA3 gene polymorphisms and haplotypes alone do not appear to be major risk factors for HDPs or sPE/HELLP.
• Parent-of-origin effects, particularly concerning rs4934 inheritance, suggest potential maternal-fetal genomic incompatibility in pregnancy disorders.