Variants of the Progesterone Receptor Gene as Modulators of Risk for Idiopathic Spontaneous Premature Birth

Premature birth (PTB) is the most common cause of perinatal mortality and morbidity. We performed a case-control study to determine whether two selected single-nucleotide polymorphisms (SNPs) of the progesterone receptor gene (<i>PGR</i>) (rs4754732 and rs653752) play a role in the modulation of the risk for spontaneous PTB. This study included 400 mothers (199 with premature delivery and 201 with term delivery) and 400 newborns (201 term-born and 199 premature-born) of European descent. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. We found no statistically significant difference in the distribution of genotypes and allele frequencies between prematurely born newborns and newborns at term for either investigated SNP. There was no statistically significant difference in the distribution of genotypes and allele frequencies between groups of mothers with extremely early and early PTB compared to the group of mothers with term births. Potential association of the mothers' C allele of rs653752 with lower odds of PTB (<i>p</i> = 0.03; odds ratio 1.36; 95% confidence interval 1.02-1.81; Chi-square test), and association of the mothers' CC genotype of rs653752 in the recessive inheritance model with lower odds of PTB in general (<i>p</i> = 0.02; odds ratio 0.54; 95% confidence interval 0.32-0.91; Chi-square test) and with a late PTB (<i>p</i> = 0.005, odds ratio 0.45, 95% confidence interval 0.23-0.79; Chi-square test), were found. It was also found that the mothers who were carriers of the haplotype T-G combination of rs4754732 and rs653752 were 1.5 times more likely to have PTB, even after correcting the <i>p</i>-value for multiple comparisons (<i>p</i> = 0.008; odds ratio 1.59; 95% confidence interval 1.13-2.24, Chi-square test). Further research on a larger number of subjects of these and other <i>PGR</i> SNPs will be needed in order to confirm the presented results.