Date Published: January 14, 2010
Publisher: Public Library of Science
Author(s): Meka Aruna, Theeya Nagaraja, Sadaranga Andal, Surapaneni Tarakeswari, Pisapati V. S. Sirisha, Alla G. Reddy, Kumarasamy Thangaraj, Lalji Singh, B. Mohan Reddy, Syed A. Aziz. http://doi.org/10.1371/journal.pone.0008712
Abstract: 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.
Partial Text: Recurrent Spontaneous Abortions (RSA) is defined as repeated occurrence of 3 or more miscarriages before 24th week of gestation . The modern definition, however, is the spontaneous loss of 2 or more consecutive pregnancies before 20 weeks of gestation , . Implantation of the embryo is a critical event in pregnancy. In humans, peri-implantation pregnancy loss contributes to more than 20% of unexplained infertility. Deficient hormone levels result in aberrant growth and support of the uterine lining making it un-ideal for implantation.
We did not find any new SNPs in hPR gene, other than the 3 found earlier. The three SNPs found in the PR gene – exon 1: G 1031 C, S344T; exon 4: G 1978 T, L660V; exon 5: C 2310 T, H770H – co-inherit. The genotype frequencies of the homozygotes for wild type allele (*1), heterozygotes (*1/*2) and homozygotes for the rarer mutant allele (*2) in the RSA women were observed to be 127 (88.8%), 15 (10.5%) and 1(0.7%), respectively, as compared to 122 (81.3%), 25 (16.7%), and 3(2%) in controls (Figure 1). The genotype frequencies were not significantly different between RSA and control women (χ2 = 3.44, df = 2, p = 0.18).
Progesterone receptor mediated effects play a critical role in female reproduction –, –. We investigated mutations of the progesterone receptor gene and observed an increased frequency of the *2 allele in the controls (10.3%) when compared to the RSA women (5.9%). The frequency of 2.7% of the T2 allele in the controls in our study is relatively close to the frequency of 5.5% among the normal women from Hyderabad . In our study, 3 women in the control group were homozygous for the *2 allele, yet they had no abortions suggesting that even the homozygous mutations are not sufficient to cause RSA. Haploview analysis suggests that even though the three SNPs show a D′ of 1, the LD block consists of the SNPs in the exons 4 and 5 only. Based on our genotyping results, we find that the insertion (T2 allele) is seen only among the individuals with at least one copy of the *2 allele suggesting a possible association between the *2 allele and the T2 allele, which is in concordance with the results of Haploview analysis revealing a partial LD.