Association of the PECAM-1 (Leu125Val) and P-Selectin (Thr715Pro) Gene Polymorphisms With Unexplained Spontaneous Miscarriages

Overview

Journal Cureus

Specialty Biomedical Engineering

Date 2022 Mar 11

PMID 35273840

Authors

Nikolaos Vlachadis

Vassilios Tsamadias

Maria Siori

Nikolaos Vrachnis

Emmanuel Economou

Affiliations

Soon will be listed here.

Abstract

Introduction: The aim of this study was to investigate the possible effect of the PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms in unexplained spontaneous abortions.

Methods: In a case-control design, Greek nulligravida women with recurrent idiopathic miscarriages <20 weeks of gestation and fertile controls were genotyped by pyrosequencing.

Results: There was no significant association of the PECAM-1-C373G (Leu125Val) polymorphism with recurrent abortions. Although the P-Selectin-A37674C (Thr715Pro) polymorphism was not associated with miscarriages overall, the association was statistically significant for younger women (carriers of the P-Selectin-37674C allele: <35 years: odds ratio (OR) = 3, 95% confidence interval (CI): 1.13-7.97, p = 0.023; <30 years: OR = 6.75, 95%CI: 2.02-22.58, p = 0.002). In comparison with CC/AA genotype, the combined carriers of the PECAM-1-373G and P-Selectin-37674C alleles had OR =8.81 (95%CI: 1.07-72.50, p = 0.024). The association of the coexistence of the two polymorphisms was stronger in younger women (<35 years: OR = 12.07, 95%CI: 1.38-105.68, p = 0.014; <30 years: OR = 65, 95%CI: 3.38-1251.28, p = 0.001), and late (OR = 10.64, 95%CI: 1.16-97.60, p = 0.024) and second-trimester miscarriages (OR = 26, 95%CI: 1.84-367.71, p = 0.014). The association between carriage of the P-Selectin-37674C allele and recurrent miscarriages was significant for younger women.

Conclusion: The coexistence of the PECAM-1-373G and P-Selectin-37674C alleles increased the miscarriage risk for the total population studied, suggesting an interaction between the two polymorphisms, more pronouncedly in younger women and the association was stronger for late fetal loss.

Citing Articles

Platelet Glycoprotein Receptor Ia-C807T and IIIa-PlA1/PlA2 Genetic Polymorphisms Are Associated With Enhanced Platelet Function in Women With Recurrent Miscarriages.

Tsamadias V, Vlachadis N, Demeridou S, Kouskouni E, Creatsas G, Vlahos N Cureus. 2023; 15(10):e47832.

PMID: 37899902 PMC: 10611447. DOI: 10.7759/cureus.47832.

The roles of P-selectin in cancer cachexia.

Ling T, Liu J, Dong L, Liu J Med Oncol. 2023; 40(11):338.

PMID: 37870739 DOI: 10.1007/s12032-023-02207-2.

Circulating and Endometrial Profiles of miR-145, miR-155-5p, miR-224, MPP-5, and PECAM-1 Expression in Patients with Repeated Implantation Failure: A Case Control Study.

Jahanbakhsh J, Farid Mojtahedi M, Moradi N, Fadaei R, Tehranian A, Rostami R Cell J. 2023; 25(6):427-436.

PMID: 37434460 PMC: 10331447. DOI: 10.22074/cellj.2023.1988609.1218.

Platelet distribution width and the risk of unexplained recurrent pregnancy loss: a meta-analysis.

Shi Y, Xu D J Assist Reprod Genet. 2023; 40(7):1523-1531.

PMID: 37227569 PMC: 10352223. DOI: 10.1007/s10815-023-02819-7.

Human Leukocyte Antigen Alleles Compatibility and Immunophenotypic Profile Associations in Infertile Couples.

Oikonomou G, Vlachadis N, Tsamadias V, Lambrinoudaki I, Deligeoroglou E, Vlahos N Cureus. 2023; 15(3):e36584.

PMID: 36968684 PMC: 10035384. DOI: 10.7759/cureus.36584.

References

Quaranta M, Erez O, Mastrolia S, Koifman A, Leron E, Eshkoli T . The physiologic and therapeutic role of heparin in implantation and placentation. PeerJ. 2015; 3:e691. PMC: 4304855. DOI: 10.7717/peerj.691. View

Guo F, Si C, Zhou M, Wang J, Zhang D, Leung P . Decreased PECAM1-mediated TGF-β1 expression in the mid-secretory endometrium in women with recurrent implantation failure. Hum Reprod. 2018; 33(5):832-843. DOI: 10.1093/humrep/dey022. View

Geng J, Chen M, Chou K . P-selectin cell adhesion molecule in inflammation, thrombosis, cancer growth and metastasis. Curr Med Chem. 2004; 11(16):2153-60. DOI: 10.2174/0929867043364720. View

Kupferminc M . Thrombophilia and pregnancy. Reprod Biol Endocrinol. 2003; 1:111. PMC: 305329. DOI: 10.1186/1477-7827-1-111. View

Gu Y, Wang J, Zhang Z, Wang J, Cao Y, Pan C . The association between polymorphisms of genes related to inflammation and recurrent pregnancy loss. Gynecol Endocrinol. 2017; 34(4):349-352. DOI: 10.1080/09513590.2017.1395837. View

Achache H, Revel A . Endometrial receptivity markers, the journey to successful embryo implantation. Hum Reprod Update. 2006; 12(6):731-46. DOI: 10.1093/humupd/dml004. View

Li G, Han Z, Dong H, Zhang X, Kong X, Jin X . Platelet endothelial cell adhesion molecule-1 gene 125C/G polymorphism is associated with deep vein thrombosis. Mol Med Rep. 2015; 12(2):2203-10. DOI: 10.3892/mmr.2015.3586. View

Kolte A, Bernardi L, Christiansen O, Quenby S, Farquharson R, Goddijn M . Terminology for pregnancy loss prior to viability: a consensus statement from the ESHRE early pregnancy special interest group. Hum Reprod. 2014; 30(3):495-8. DOI: 10.1093/humrep/deu299. View

Dendana M, Hizem S, Magddoud K, Messaoudi S, Zammiti W, Nouira M . Common polymorphisms in the P-selectin gene in women with recurrent spontaneous abortions. Gene. 2011; 495(1):72-5. DOI: 10.1016/j.gene.2011.11.034. View

10.

Daher S, Mattar R, Gueuvoghlanian-Silva B, Torloni M . Genetic polymorphisms and recurrent spontaneous abortions: an overview of current knowledge. Am J Reprod Immunol. 2012; 67(4):341-7. DOI: 10.1111/j.1600-0897.2012.01123.x. View

11.

Mor G, Cardenas I, Abrahams V, Guller S . Inflammation and pregnancy: the role of the immune system at the implantation site. Ann N Y Acad Sci. 2011; 1221:80-7. PMC: 3078586. DOI: 10.1111/j.1749-6632.2010.05938.x. View

12.

. Evaluation and treatment of recurrent pregnancy loss: a committee opinion. Fertil Steril. 2012; 98(5):1103-11. DOI: 10.1016/j.fertnstert.2012.06.048. View

13.

Vlachadis N, Tsamadias V, Vrachnis N, Kaparos G, Vitoratos N, Kouskouni E . Associations of combined polymorphisms of the platelet membrane glycoproteins Ia and IIIa and the platelet-endothelial cell adhesion molecule-1 and P-Selectin genes with IVF implantation failures. J Obstet Gynaecol. 2017; 37(3):363-369. DOI: 10.1080/01443615.2016.1256978. View

14.

Woodfin A, Voisin M, Nourshargh S . PECAM-1: a multi-functional molecule in inflammation and vascular biology. Arterioscler Thromb Vasc Biol. 2007; 27(12):2514-23. DOI: 10.1161/ATVBAHA.107.151456. View

15.

Andreotti F, Porto I, Crea F, Maseri A . Inflammatory gene polymorphisms and ischaemic heart disease: review of population association studies. Heart. 2002; 87(2):107-12. PMC: 1766990. DOI: 10.1136/heart.87.2.107. View

16.

Kwak-Kim J, Yang K, Gilman-Sachs A . Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res. 2009; 35(4):609-22. DOI: 10.1111/j.1447-0756.2009.01079.x. View

17.

Han A, Han J, Lee S . Inherited thrombophilia and anticoagulant therapy for women with reproductive failure. Am J Reprod Immunol. 2020; 85(4):e13378. DOI: 10.1111/aji.13378. View

18.

Vlachadis N, Tsamadias V, Vrachnis N, Kaparos G, Vitoratos N, Kouskouni E . Genetic heterogeneity of platelet glycoproteins Ia and IIIa and the risk of spontaneous miscarriages. J Matern Fetal Neonatal Med. 2016; 30(11):1309-1313. DOI: 10.1080/14767058.2016.1212330. View

19.

Li M, Huang S . Innate immunity, coagulation and placenta-related adverse pregnancy outcomes. Thromb Res. 2009; 124(6):656-62. PMC: 2788065. DOI: 10.1016/j.thromres.2009.07.012. View

20.

Vlachadis N, Tsamadias V, Kouskouni E, Vitoratos N, Hatziveis K, Economou E . Genetic heterogeneity of platelet glycoproteins Ia and IIIa is associated with in vitro fertilisation implantation failure. J Obstet Gynaecol. 2015; 35(7):733-6. DOI: 10.3109/01443615.2015.1004528. View