Role of progesterone receptor polymorphisms in the recurrent spontaneous abortions: Indian case

Abstract

Background: We 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 findings: A 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/significance: The 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.

Figure 1. Genotype distribution of the PR mutations; (*1) wild type (G1031, G1978, and C2310) and (*2) mutant allele.

Figure 2. Genotype distribution of PROGINS insertion; (T1) wild type (no insertion) and (T2) insertion allele.

Figure 3. LD plot showing the confidence bounds color scheme where dark grey suggests strong evidence of LD and light grey suggests an uninformative status of LD.

The analysis reveals that exons 4 and 5 inherit as an LD Block.

Figure 4. Electropherograms of the two SNPs of hPR gene in exon 1 (G1031C) and exon 4 (G1978T).

Figure 5. Gel picture showing bands for homozygotes (T1) allele, heterozygotes (T1/T2), and homozygote (T2) allele run on 2% agarose.

Lane 3, 4, 5, and 6 are heterozygotes, and lane 13 is homozygous for the T2 allele and the remaining are homozygous for the T1 allele.