Jelena Milenkovic1, Maja Milojkovic2, Dejan Mitic3, Tatjana Jevtovic Stoimenov4, Zaklina Smelcerovic5, Dijana Stojanovic2, Stevan Vujic5, Novica Bojanic5. 1. Department of Pathophysiology, Faculty of Medicine, University of Nis, Nis, Serbia. jelenaradovic982@gmail.com. 2. Department of Pathophysiology, Faculty of Medicine, University of Nis, Nis, Serbia. 3. Gyneacology and Obstetrics Clinic, Clinical Center in Nis, University of Nis, Nis, Serbia. 4. Department of Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia. 5. Scientific Research Center for Biomedicine, Faculty of Medicine, University of Nis, Nis, Serbia.
Abstract
PURPOSE: Our aim was to evaluate the frequency and SNP-SNP interactions between factor V Leiden (FVL) G1691A, prothrombin G20210A mutation, and C677T MTHFR and PAI-1 4G/5G gene polymorphisms in female IVF patients with unexplained infertility (UI) by using a multifactor dimensionality reduction (MDR) model analysis. METHODS: A total of 225 subjects were enrolled in the study. There were 105 females in UI group and 120 healthy controls. Designated SNPs were determined by using allele-specific PCR methods. The difference in thrombophilia prevalence was assessed by a chi-square test and logistic regression analysis. Four-locus SNP interaction model was tested using the MDR approach. A ten-fold cross-validation consistency (CVC) and permutation testing were performed. RESULTS: There was a significant difference of MTHFR C677T polymorphism frequency between the groups. Significantly less UI patients had MTHFR CC genotype (p = 0.005), while the risk allele T was more frequent (OR = 1.83, p = 0.0018). Logistic regression determined a significant association only for MTHFR C677T in our patients (TT genotype OR = 2.99). The MDR analysis confirmed the significance of a single-locus model for MTHFR C677T polymorphism (p = 0.015; OR = 2.93). However, the best, significant predictive model was the two-locus model comprising MTHFR C677T and FVL (CVC = 10/10, testing accuracy = 60.95%, p = 0.013; OR = 3.02). CONCLUSION: The MTHFR C677T polymorphism was significantly associated with UI, with minor allele T being more frequent. Additionally, there was a significantly increased presence of MTHFR C677T with FVL mutation in these patients. Therefore, MTHFR and its interaction with FVL should be recognized as contributing factors in the pathogenesis of infertility.
PURPOSE: Our aim was to evaluate the frequency and SNP-SNP interactions between factor V Leiden (FVL) G1691A, prothrombinG20210A mutation, and C677TMTHFR and PAI-1 4G/5G gene polymorphisms in female IVFpatients with unexplained infertility (UI) by using a multifactor dimensionality reduction (MDR) model analysis. METHODS: A total of 225 subjects were enrolled in the study. There were 105 females in UI group and 120 healthy controls. Designated SNPs were determined by using allele-specific PCR methods. The difference in thrombophilia prevalence was assessed by a chi-square test and logistic regression analysis. Four-locus SNP interaction model was tested using the MDR approach. A ten-fold cross-validation consistency (CVC) and permutation testing were performed. RESULTS: There was a significant difference of MTHFRC677T polymorphism frequency between the groups. Significantly less UI patients had MTHFR CC genotype (p = 0.005), while the risk allele T was more frequent (OR = 1.83, p = 0.0018). Logistic regression determined a significant association only for MTHFRC677T in our patients (TT genotype OR = 2.99). The MDR analysis confirmed the significance of a single-locus model for MTHFRC677T polymorphism (p = 0.015; OR = 2.93). However, the best, significant predictive model was the two-locus model comprising MTHFRC677T and FVL (CVC = 10/10, testing accuracy = 60.95%, p = 0.013; OR = 3.02). CONCLUSION: The MTHFRC677T polymorphism was significantly associated with UI, with minor allele T being more frequent. Additionally, there was a significantly increased presence of MTHFRC677T with FVL mutation in these patients. Therefore, MTHFR and its interaction with FVL should be recognized as contributing factors in the pathogenesis of infertility.
Entities:
Keywords:
Epistasis; Factor V Leiden; In vitro fertilization; Methylenetetrahydrofolate reductase; PAI-1 4G/5G; Prothrombin G20210A mutation
Authors: J C Gris; S Ripart-Neveu; C Maugard; M L Tailland; S Brun; C Courtieu; C Biron; M Hoffet; B Hédon; P Marès Journal: Thromb Haemost Date: 1997-06 Impact factor: 5.249