Genetic risk factors for venous thromboembolism among infertile men with Klinefelter syndrome

• Published in: Journal of clinical & translational endocrinology Vol. 20; p. 100228
• Main Authors: Hussein, Tarek M., Abd Elmoaty Elneily, Dalia, Mohamed Abdelfattah Elsayed, Fatma, El-Attar, Lama M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.06.2020; Elsevier
• Subjects: Allele frequency; Genotype; Hereditary thrombophilia; Klinefelter syndrome; Polymorphism; Research Paper; VTE, thrombosis; Klinefelter syndrome; PTH; VTE; MTHFR; Genotype; Hereditary thrombophilia; PROCR; HDL; MAF; Allele frequency; APC; SNP; LDL; PAI-1; EPCR; FSH; LH; VTE, thrombosis; FV Leiden; BMI; Polymorphism; FV Leiden, Factor V leiden; MAF, Minor Allele Frequency; BMI, Body mass index; PROCR, Protein C receptor gene; LH, Luteinizing hormone; PTH, Prothrombin; MTHFR, 5, 10-methylene tetrahydrofolate reductase; PAI-1, plasminogen activator inhibitor 1; FSH, Follicle stimulating hormone; LDL, Low density lipoprotein; SNP, Single Nucleotide Polymorphism; EPCR, Endothelial protein C receptor; VTE, Venous thromboembolism; APC, activated protein C; HDL, High density lipoprotein
• ISSN: 2214-6237; 2214-6237
• DOI: 10.1016/j.jcte.2020.100228

•Infertile males with KS have sex-chromosome abnormalities, endocrinal disturbances and other health problems.•Hereditary thrombophilia may exacerbate tendency to thrombosis in KS patients.•Genotype and allele frequency of thrombophilic gene variants were remarkably high in men with KS.•The coexistence of different mutant alleles was evident in infertile KS males. Klinefelter syndrome (KS) is one of the commonest sex chromosome disorders. Affected males become infertile and highly susceptible to several health problems, including vascular thromboembolism (VTE). The risk of VTE may be exacerbated by an underlying genetically inherited thrombophilia. In this study, we aimed to investigate the genotype and allele frequencies of common gene polymorphisms related to hereditary thrombophilia in infertile males with KS compared to normal, fertile men. Eighty-five infertile males with KS and 75 healthy control males were included in this case-control study. Genetic testing was done using an extended thrombophilia gene panel by Multiplex PCR reverse hybridization method. There was an increased frequency of mutant alleles and heterozygous genotypes of FV Leiden, FV H 1299R, Pro G20210A, MTHFR C677T and PAI-1 4G/5G thrombophilic gene polymorphisms in KS patients compared to the control group. It was shown that 10.7% of KS patients had the A3 haplotype of the EPCR gene in comparison to 5.3% of control patients. The A3/A3 genotype was found only in KS patients (7.1%). Carriers of more than one mutant allele in KS patients exceeded the control (p < 0.001). A high prevalence of thrombophilic gene polymorphisms and the coexistence of different mutant alleles were evident in infertile KS males. These data highlight the importance of conducting further studies to understand the role of hereditary thrombophilia in predicting venous thrombosis in patients with Klinefelter syndrome.