Both Fetal and Maternal Genotypes Affect Preeclampsia Pathogenesis in Iranian Patients

Area of Science:

• Genetics
• Obstetrics
• Reproductive Medicine

Background:

• Preeclampsia is a pregnancy-specific disorder with complex genetic underpinnings.
• Genome-wide association studies (GWASs) have identified potential preeclampsia susceptibility variants in diverse populations.
• Replication of GWAS findings in different ethnicities is crucial for validating genotype-phenotype associations.

Purpose of the Study:

• To investigate the association of three previously reported GWAS signals (FLT1 rs4769612, FTO rs1421085, ZNF831 rs259983) with preeclampsia in the Iranian population.
• To perform a replication study to confirm genotype-phenotype associations in a distinct ethnic group.

Main Methods:

• A case-control study involving 600 subjects: 200 preeclamptic patients, 200 healthy pregnant women, 100 neonates from preeclamptic pregnancies, and 100 neonates from healthy pregnancies.
• Genotyping of single nucleotide polymorphisms (SNPs) rs4769612, rs1421085, and rs259983 using the tetra-primer amplification refractory mutation system-polymerase chain reaction (TP-ARMS PCR) technique.
• Statistical analysis to assess the association of fetal and maternal genotypes with preeclampsia risk under different inheritance models (recessive, dominant, over-dominant).

Main Results:

• The fetal genotype of FLT1 rs4769612 was associated with preeclampsia risk under a recessive inheritance model.
• The fetal genotype of FTO rs1421085 increased preeclampsia risk under dominant and over-dominant inheritance models.
• Maternal ZNF831 rs259983 genotype was associated with preeclampsia under the dominant model, while no association was found with fetal genotype.

Conclusions:

• The study successfully replicated associations of FLT1 rs4769612, FTO rs1421085, and ZNF831 rs259983 with preeclampsia risk in the Iranian population.
• Specific genetic variants in FLT1, FTO, and ZNF831 contribute to preeclampsia susceptibility in this ethnic group.
• Despite some discrepancies with previous studies, the findings highlight the role of these polymorphisms in preeclampsia pathogenesis.