Role of Progesterone Receptor Polymorphisms in the Recurrent Spontaneous Abortions: Indian Case

Abstract

BackgroundWe attempt to ascertain if the 3 linked single nucleotide polymorphisms (SNPs) of the Progesterone Receptor (PR) gene (exon 1: G 1031 C; S344T, exon 4: G 1978 T; L660V and exon 5: C 2310 T; H770H) and the PROGINS insertion in the intron G, between exons 7 and 8, are associated with Recurrent Spontaneous Abortion (RSA) in the Indian population.Methodology/Principal FindingsA total of 143 women with RSA and 150 controls were sequenced for all the 8 exons looking for the above 3 linked SNPs of the PR gene earlier implicated in the RSA, as well as for any new SNPs that may be possibly found in the Indian population. PROGINS insertion was screened by electrophoresis. We did not find any new mutations, not observed earlier, in our population. Further, we did not find significant role of the *2 allele (representing the mutant allele at the three SNP loci) or the T2 allele (PROGINS insertion) in the manifestation of RSA. We also did not find an LD pattern between each of the 3 SNPs and the PROGINS insertion.Conclusions/SignificanceThe results suggest that the PR gene mutations may not play any exclusive role in the manifestation of RSA, and instead, given significantly higher frequency of the *2 allele among the normal women, we surmise if it does not really confer a protective role among the Indian populations, albeit further studies are required in the heterogeneous populations of this region before making any conclusive statement.

Association of progesterone receptor gene polymorphism with male infertility and clinical outcome of ICSI

“…Bidirectional sequencing of the PR coding region identified four SNPs of which rs3740753, rs104283 and rs104283 are in complete linkage disequilibrium. Referred to as *2 allele, these SNPs have been previously reported and occur at frequencies nearly identical to that reported in the Indian population [5]. However, the genotypic or allelic frequencies of *2 were not significantly different between normozospermic controls vs oligozoopsermic or azoopsermic or infertile normozoospermc.…”

“…While there are reports that have refuted these findings [5,23], the influence of maternal genome on embryonic growth cannot be underestimated. Beyond the maternal genome, evidences are now available where the paternal genome has also been suggested to influence embryogenesis.…”

“…PCR was performed at an optimized annealing temperature and has been detailed elsewhere [1,5,40]. The amplicons were further subjected to direct sequencing [5,40] using BigDye Terminator cycle sequencing kit (Applied Biosystems, Foster City USA) and 3730 DNA analyzer (Applied Biosystems). The PROGINS amplified products were loaded in a 2 % agarose gel stained with ethidium bromide and observed under UV transillumination ( Fig.…”

Association of progesterone receptor polymorphism with idiopathic recurrent pregnancy loss in Taiwanese Han population

“…PGR polymorphisms were reported to be associated with adverse reproductive outcomes, including unexplained infertility [19], repeated IVF implantation failure [20] and unexplained RPL [8][9][10], although the results were not consistent. Three articles have been published to explore the association between the PGR polymorphism and recurrent miscarriage [8][9][10].…”

“…To date, three reports on different ethnicities have been published to explore the association between the PGR polymorphism and recurrent miscarriage, but the study designs were different and the results were inconsistent [8][9][10]. Considering the important role of PGR in regulating human early pregnancy, but the contradictory results of the genetic association studies, this study was conducted, for the first time, using tag SNPs and haplotype analysis to investigate the association between polymorphisms of PGR and idiopathic RPL.…”