Progesterone receptor genetic variants in pregnant women and fetuses as possible predictors of spontaneous premature birth: A preliminary case–control study

Abstract

Aim: To evaluate the roles of four selected genetic variations in fetal and maternal progesterone receptor gene (PGR) and to identify women who may have higher or lower odds for spontaneous premature birth compared to the general population. Methods: A preliminary case-control study with two groups of pregnant women (with term and premature delivery, 218 in total) and two groups of newborns (term and preterm, 218 in total) was performed. Four single nucleotide polymorphisms (SNPs) of the progesterone receptor gene (rs1042838, rs1042839, rs10895068, and rs1942836) were genotyped. Results: There was statistically significant difference between cases and controls in the distribution of newborns' allele frequency of minor C allele of the PGR SNP rs1942836 (p = 0.03, Fishers' exact test) in favor of premature birth. A statistically significant difference between the frequency of the mothers' minor T allele of rs1042838 (p = 0.005; chi-squared test) and the mothers' minor T allele of rs1042839 (p = 0.005; chi-squared test) in favor of extremely premature birth has been found. There was a statistically significant difference between the frequency of the newborns' minor C allele of rs1942836 (p = 0.03; chi-squared test) and newborns' heterozygotes CT genotype of rs1942836 (p = 0.03; Fishers' exact test) when comparing the group of term births and the group of early premature birth. Conclusion: Our study suggests that patients with selected genetic variants of the progesterone receptor gene could have greater odds for premature birth compared to term birth. Replication studies with a larger population and different ethnicity are needed in order to confirm these findings.

The Role of Genetics in Preterm Birth

“…Polymorphisms within genes encoding fibroblast growth factors 1 and 4, both involved in embryonic development, morphogenesis, cell growth, and angiogenesis, have demonstrated associations with sPTB in maternal and infant samples [ 68 , 87 , 97 ]. Genes encoding parturition-related hormones including progesterone, follicle-stimulating hormone, corticotrophin-releasing hormone, and relaxin have also been implicated in candidate genes studies [ 98 – 104 ]. Kim et al (2013) analyzed approximately 650 case-parents triads; maternal genetic effect analyses identified SNPs within leucyl and cysteinyl aminopeptidase gene ( LNPEP ) associated with prematurity .…”