Association of genetic variants of PD1 with recurrent pregnancy loss

Abstract

PurposeProgrammed cell death 1 (PD1) and PD ligand 1 (PDL1) are speculated to have an important role in maintaining a normal pregnancy and there are also a few reports of an association between the single‐nucleotide polymorphisms (SNPs) of PD1 or PDL1 and diseases in humans. The association was examined between the polymorphisms of PD1,PDL1,CTLA4 and recurrent pregnancy loss (RPL).MethodsThe study group consisted of 243 women with two or more pregnancy losses and 176 parous women. The frequency of three SNPs of PD1, two of PDL1, and four of CTLA4 were compared between the patients and controls. Next, the subsequent live birth rates in the patients with RPL with and without risk alleles were examined.ResultsTwo SNPs (rs36084323 and rs3481962) of PD1 were found to occur at significantly higher frequencies in the patient group than in the control group. The subsequent live birth rate of the patients with vs. without the risk alleles of rs36084323 and rs3481962 were 83.3% vs. 83.3% and 81.6% vs. 84.0%, respectively.ConclusionVariations of the PD1 gene were identified as risk factors for RPL. However, the presence or absence of the PD1 risk alleles had no predictive effect on the subsequent pregnancy outcome.

Next generation of immune checkpoint molecules in maternal‐fetal immunity*

“…53,54 Two SNPs (rs36084323 and rs3481962) of PD-1 have been found to occur at significantly higher frequencies in the RPL group. 55 However, there is no evidence that the presence of the PD-1 risk allele is a predictive marker of subsequent pregnancy outcomes.…”

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“…In addition, men who develop hypogonadism and low testosterone also face challenges with reproductive fitness, as exogenous testosterone inhibits spermatogenesis . It is speculated that PD1 plays a role in the maintenance of pregnancy, and single‐nucleotide sequence variants of the PD1 gene have been identified in women with recurrent pregnancy loss . Long‐term fertility studies after therapy are lacking because of the brief duration of clinical use of these agents.…”

“…36 It is speculated that PD1 plays a role in the maintenance of pregnancy, 37,38 and single-nucleotide sequence variants of the PD1 gene have been identified in women with recurrent pregnancy loss. 39 Long-term fertility studies after therapy are lacking because of the brief duration of clinical use of these agents. Vemurafenib has been reported to lead to intrauterine growth retardation when administered during pregnancy, 40 which may be related to the central role that the mitogen-activated protein kinase pathway plays in trophoblast proliferation.…”

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“…PD-1.1 (rs36084323) has been considered in a case of breast cancer [21], epithelial ovarian cancer [22] esophageal cancer [20], NSCLC [23], overall cancer risk [24], RA [16] pregnancy losses [25] and aplastic anemia [26]. Therefore, significantly lower frequencies of PD-1.1 GG have been presented in women with breast cancer [21].…”

“…For autoimmune diseases, such as RA, rs36084323 decreased an inadequate response to conventional synthetic disease-modifying antirheumatic drugs [16]. Hayashi Y. et al have evaluated the association of genetic variants of PD1 with recurrent pregnancy loss with significantly higher frequencies of rs36084323 in women with two or more pregnancy losses [25]. Polymorphism of PD-1.1 has been rare in the case of patients with aplastic anaemia [26].…”