Functionally significant polymorphisms of ESR1and PGR and risk of intrauterine growth restriction in population of Central Russia.

Objective: This study aimed to investigate the role ofESR1 and PGR gene polymorphisms in development of intrauterine growth restriction (IUGR) among Russian women in Central Russia.

Study Design: This case-control study recruited a total of 520 women in the third trimester of pregnancy, including 196 IUGR patients and 324 controls. The participants were unrelated women of self-reported Russian ethnicity. Participants were genotyped at 4 functionally significant polymorphisms of theESR1 (rs2234693, rs9340799) and the PGR (rs484389, rs1042838) genes. The association analysis was performed using logistic regression. Two polymorphisms, which were associated with IUGR, and 26 polymorphisms linked to them (r≥0.6) were analyzed for their functional significance in silico.

Results: Haplotype TG of loci rs2234693-rs9340799ESR1 (OR = 1.94, р = 0.006) was associated with an increased risk of IUGR. Allele T of rs2234693 decreases expression of ESR1 in thyroid gland, allele T of rs2234693 and allele G of rs9340799 increase affinity to eight transcription factors (AP-4, HEN1, E2A, LBP-1, RP58, LUN, Ets and Hand). The loci that are linked (r≥0.6) to the IUGR-associated SNPs, have the cis-eQTL value (expression ESR1 in thyroid gland) and showed their regulatory effects in organs and tissues related to pathogenesis of IUGR.

Conclusion: Haplotype TG defined by polymorphisms rs2234693-rs9340799 of theESR1 gene is associated with the development of IUGR in Russian women from Central Russia.