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

Vlachadis, Nikolaos; Tsamadias, Vassilios; Siori, Maria; Vrachnis, Nikolaos; Economou, Emmanuel

doi:10.7759/cureus.21859

Cited by 4 publications

(2 citation statements)

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“…We have previously reported that genetic heterogeneity of platelet glycoproteins Ia and IIIa associated with platelet-derived thrombophilia is a risk factor for recurrent IVF-ET failures [ 23 ], and subsequently, this finding was also confirmed for spontaneous miscarriages [ 24 ]. Similarly, the associations of proinflammatory PECAM-1 (Leu125Val) and P-Selectin (Thr715Pro) gene polymorphisms with unexplained spontaneous miscarriages as well as IVF-ET failures have been reported [ 25 , 26 ]. In the present study, we discovered a similar immunophenotypic and immunogenetic profile in women who miscarried and those who failed to implant, with increased levels of NK lymphocytes and CD4/CD8 ratio, a high prevalence of HLA-DQA1*5 allele and elevated HLA compatibility between spouses, as well as positive correlations between these parameters.…”

Section: Discussionmentioning

confidence: 99%

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

Oikonomou¹,

Vlachadis²,

Tsamadias³

et al. 2023

Cureus

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Introduction: The maternal immune system has a major role in the successful embryo implantation and maintenance of the pregnancy. This study aimed to investigate the maternal immunophenotyping profile (percentage of Natural Killer [NK] cells and the CD4/CD8 [cluster designation] ratio in peripheral blood lymphocytes) and the HLA (Human Leukocyte Antigen)-DQA1 alleles sharing in infertile couples. Methods: This cross-sectional study included 78 women who had experienced at least two spontaneous miscarriages and 110 women with a history of recurrent implantation failures after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF-ET failures). The NK cell percentage and the CD4/CD8 ratio were determined by flow cytometry. Genotyping of the HLA-DQA1 alleles was carried out for all women and their partners, and couple HLA-DQA1 compatibility was expressed as the percentage of common HLA-DQA1 alleles (totaling 35 alleles) shared between spouses to the sum of the unique alleles observed. Results: In women with recurrent miscarriages, high values (%) of the NK population with a median (interquartile range [IQR]) of 10.3% (7.7% to 12.5%) and CD4/CD8 ratio (1.7) (1.5 to 2.1) were found. In women with IVF-ET failures, the (%) NK population (10.5%) (8.6% to 12.5%) and CD4/CD8 ratio (1.8) (1.5 to 2.1) were similarly increased (p=0.390, and p=0.490, respectively). The proportion of women with >10% NK cells was 53.8% and 58.2% in women with miscarriages and IVF-ET failures, respectively (p=0.554). The prevalence of HLA-DQA1*5 allele carriage was elevated in women with miscarriages as well as those with IVF-ET failures (52.6% and 61.8%, respectively; p=0.206). The proportion of couples with high (>50%) HLA-DQA1 sharing was 65.4% in the group with miscarriages and 73.6% in the group with IVF-ET failures, respectively (p=0.222). The CD4/CD8 ratio was statistically significantly positively correlated with the (%) NK population in women with IVF-ET failures (rho = 0.297, p=0.002) and with the (%) HLA-DQA1 sharing in the group with miscarriages (rho = 0.266, p=0.019). The couples in which both spouses were carriers of the HLA-DQA1*5 allele had an increased probability of high (>50%) HLA-DQA1 compatibility compared with the couples in which neither of the spouses carried the allele in the miscarriage group (OR = 24.3, 95% CI: 3.0 to 198.9, p<0.001), and the IVF-ET failure group (OR = 10.5, 95% CI: 2.2 to 49.8, p<0.001). Conclusion: The peripheral NK (%) population and CD4/CD8 ratio, as well as the prevalence of the HLA-DQA1*5 allele, were elevated in women with recurrent miscarriages and IVF-ET failures. Furthermore, these couples with negative reproductive outcomes had a high percentage of HLA-DQA1 allele similarity. The presence of the HLA-DQA1*5 allele in spouses was strongly associated with overall couple HLA-DQA1 compatibility, implying that it could be used as a surrogate marker for assessing overall immunological compatibility in infertile co...

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Section: Discussionmentioning

confidence: 99%

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

Oikonomou¹,

Vlachadis²,

Tsamadias³

et al. 2023

Cureus

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“…Over the past 2-3 decades, numerous studies have reported on the role of genetic polymorphisms in the etiopathogenesis of recurrent miscarriages, with particular emphasis on the role of genetic thrombophilia [6][7][8]. Possible biological mechanisms explaining the role of genetic thrombophilia in the incidence of miscarriage include impaired blood supply to the fetus in early pregnancy and abnormal placentation [9].…”

Section: Introductionmentioning

confidence: 99%

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

Tsamadias,

Vlachadis,

Demeridou

et al. 2023

Cureus

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Introduction: Thrombophilic genetic polymorphisms of the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa) have been associated with an increased risk of recurrent miscarriages. The aim of this study was to investigate the association of genetic polymorphisms GpIa-C807T and GpIIIa-T1565C-PlA1/PlA2 with platelet function in women with unexplained spontaneous recurrent miscarriages.Methods: This cross-sectional study comprised 196 unrelated nulliparous Greek women with a history of unexplained recurrent miscarriages. Patients were genotyped for the presence of the GpIa-C807T (rs1126643) and GpIIIa-T1565C-PlA1/PlA2 (rs5918) genetic polymorphisms by pyrosequencing, and the collagen/epinephrine closure time (COL/EPI CT) of the subjects was assessed using the platelet function analyzer (PFA)-100.Results: In the total population of women with recurrent miscarriages, the COL/EPI CT ranged from 70 to 160 seconds (median: 122 seconds, interquartile range (IQR): 102.3-138 seconds). In comparison with the double homozygotes CC/PlA1PlA1 that had the most prolonged CT (mean: 131.9 ± 17.5 seconds), the COL/EPI CT was statistically significantly shorter for the GpIa-807T single carriers (mean: 120.3 ± 20.9 seconds) (p=0.011) (absolute difference: 11.6 seconds, 95% confidence interval (CI): 21.2 to -2.0 seconds; relative difference: -9%, 95% CI: -16% to -2%), and the GpIIIa-PlA2 single carriers also displayed a trend for shorter COL/EPI CT (mean: 121.3 ± 23.7 seconds) (p=0.141) (absolute difference: -10.6 seconds, relative difference: -8%), whereas the combined carriers of the GpIa-807T and the GpIIIa-PlA2 alleles exhibited the shortest COL/EPI CT (mean: 104.1 ± 19.7 seconds) (absolute difference: -27.7 seconds, 95% CI: -39.1 to -16.3 seconds; relative difference: -21%, 95% CI: -30% to -12%) (p<0.001). In comparing genotype frequencies in the lower half with those in the upper half of the COL/EPI CT range, the GpIa-807T and the GpIIIa-PlA2 single carriers were associated with higher odds of COL/EPI CT < 122 seconds (odds ratio (OR)=3.4, 95% CI: 1.5 to 7.5, p=0.002, and OR=2.6, 95% CI: 1.0 to 7.2, p=0.053, respectively). The association was strongest for the combined carriers with OR of 15.0 (95% CI: 5.2 to 43.2, p<0.001) for COL/EPI CT below the median and OR of 35.5 (95% CI: 4.4 to 284.5, p<0.001) for COL/EPI CT < 100 seconds. Conclusion:The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly the combined carriers of the risk variants are associated with enhanced platelet reactivity expressed via shorter COL/EPI CT. These findings provide further evidence for the role of platelet-associated genetic thrombophilia in the pathogenesis of recurrent miscarriages and promote the analysis of platelet function as a diagnostic tool in the evaluation of this disorder.

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

Shi¹,

2023

J Assist Reprod Genet

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

Cited by 4 publications

References 24 publications

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

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

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

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

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