title: 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.
abstract: The aim of the study was to investigate the combined impact of the genetic heterogeneity of the glycoproteins Ia (GpIa) and IIIa (GpIIIa) and the platelet-endothelial cell adhesion molecule-1 (PECAM-1) and P-Selectin genes on IVF embryo transfer implantation failures (IVF-ET failures). Sixty nulligravida women with previous IVF-ET failures and 60 fertile controls were genotyped for the GpIa-C807T, GpIIIa-PlA1/PA2, PECAM-1-C373G (Leu125Val) and P-Selectin-A37674C (Thr715Pro) polymorphisms by pyrosequencing. Compared with wild-type combined homozygotes, carriers of combinations of risk alleles in two gene loci were at significantly increased risk for IVF-ET failure, whereas carriers of the combination of GpIa-807T, GpIIIa-PlA2 and PECAM-1-373G alleles had OR = 52.50 (95%CI: 4.05-680.95, p < .001). The area under the receiver-operating characteristic curve (AUC) based on the number of polymorphisms and the number of risk alleles per subject was 75.4% (95%CI: 66.7%-82.8%, p < .001) and 72.5% (95%CI: 63.6%-80.3%, p < .001), respectively. The OR per polymorphism and risk allele increase was 4.26 (95%CI: 2.15-8.41, p < .001) and 2.85 (95%CI: 1.71-4.76, p < .001), respectively. The above associations were more robust among younger women. The combined analysis of these polymorphisms revealed strong association of combined carriers with IVF-ET failures especially for younger women and provided a genetic risk score with good diagnostic accuracy in the prediction of IVF-ET failures.
authors.affiliation: a Clinical Laboratory of Therapeutic Individualization, Second Department of Obstetrics and Gynecology , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vlachadis
authors.affiliation: a Clinical Laboratory of Therapeutic Individualization, Second Department of Obstetrics and Gynecology , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Vasileios
authors.initials: V
authors.lastname: Tsamadias
authors.affiliation: b Second Department of Obstetrics and Gynecology , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vrachnis
authors.affiliation: c Department of Microbiology and Biochemistry , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kaparos
authors.affiliation: b Second Department of Obstetrics and Gynecology , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Vitoratos
authors.affiliation: a Clinical Laboratory of Therapeutic Individualization, Second Department of Obstetrics and Gynecology , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.|c Department of Microbiology and Biochemistry , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Evaggelia
authors.initials: E
authors.lastname: Kouskouni
authors.affiliation: a Clinical Laboratory of Therapeutic Individualization, Second Department of Obstetrics and Gynecology , National and Kapodistrian University of Athens, School of Medicine, Aretaieio Hospital , Athens , Greece.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Economou
mesh_terms: D000328:Adult; D000367:Age Factors; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D010064:Embryo Implantation / Q000235:genetics*; D005260:Female; D005307:Fertilization in Vitro; D006579:Heterozygote; D006801:Humans; D039421:Integrin alpha2 / Q000097:blood / Q000235:genetics*; D039661:Integrin beta3 / Q000097:blood / Q000235:genetics*; D019007:P-Selectin / Q000235:genetics*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D012680:Sensitivity and Specificity; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D039421:Integrin alpha2; D039661:Integrin beta3; D019007:P-Selectin; D019408:Platelet Endothelial Cell Adhesion Molecule-1
keywords: IVF; SNP; implantation; platelets; polymorphisms; thrombophilia