RESUMEN
Vitamin D deficiency has been linked with different health problems including male infertility. Its function is mediated by the vitamin D receptor, which acts as a transcription factor. Epigenetic mechanisms such as DNA methylation may affect the vitamin D receptor gene and result in gene silencing. The present study aimed to assess serum vitamin D level and seminal methylation of vitamin D receptor gene in idiopathic male infertility. Blood and semen samples were collected from 60 men with idiopathic infertility and 40 healthy fertile men. Vitamin D levels were detected using enzyme-linked fluorescent assay technique and methylation status was assessed by methylation-specific PCR. Results revealed that serum levels of 25OHD were significantly lower in patients compared to controls. Positive correlation was found between serum level of 25OHD and sperm concentration in patients group and progressive motility in total studied group. Methylation of vitamin D receptor gene was significantly higher in patients compared to control group. Negative correlation was found between methylation of vitamin D receptor gene and both sperm concentration and progressive motility in total studied group. Results of the present study suggest that vitamin D deficiency and vitamin D receptor gene methylation may be involved in aetiopathogenesis of idiopathic male infertility.
Asunto(s)
Infertilidad Masculina , Receptores de Calcitriol/genética , Vitamina D/sangre , Metilación de ADN , Egipto/epidemiología , Humanos , Infertilidad Masculina/genética , Infertilidad Masculina/metabolismo , Masculino , Receptores de Calcitriol/metabolismo , Semen , Motilidad Espermática , Espermatozoides/metabolismoRESUMEN
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.
RESUMEN
Protamines are considered the most important structure in the sperm nucleus, and they are proteins with a significantly large amount of amino acids carrying a positive charge, which allows the formation of the tight package of the genomic DNA in the spermatozoa. Many authors studied the abnormalities in the protamine 1 (PRM1) and/or protamine 2 (PRM2) genes and reported their possible association with male infertility. The chromosome 16 (16p13.2) carries these genes containing multiple undiscovered single nucleotide polymorphisms. The aim of the present study was to investigate the association of c.-190 C>A transversions that occur in PRM1 with idiopathic infertility in a sample of Egyptian men. It was a case-control study, and blood samples were collected from sixty male patients complaining of idiopathic infertility and forty healthy fertile males. The c.-190 C>A transversion in promotor region protamine 1 gene (rs2301365) was assessed by 5' nuclease assay, using Rotor-Gene Q real-time PCR system. The results of the present study revealed that CA and AA genotypes in PRM1 gene were associated significantly with low sperm concentration and decreased sperm motility (p = 0.001). Cases carrying A allele had a 6.05-fold increased risk for idiopathic infertility than cases carrying the C allele (OR: 6.05, 95% CI: 2.038-17.98 p statistically significant ≤0.05). Analysis of the results revealed that the c.-190 C>A transversion may be involved in the development of male infertility.
Asunto(s)
Predisposición Genética a la Enfermedad , Infertilidad Masculina/genética , Regiones Promotoras Genéticas/genética , Protaminas/genética , Adulto , Alelos , Estudios de Casos y Controles , Egipto/epidemiología , Voluntarios Sanos , Humanos , Infertilidad Masculina/sangre , Infertilidad Masculina/epidemiología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Medición de Riesgo , Factores de Riesgo , Recuento de Espermatozoides , Motilidad Espermática/genética , Adulto JovenRESUMEN
BACKGROUND: Kaposi's sarcoma (KS) is an angioproliferative disorder associated with human herpesvirus 8 infection. Classic KS is the most prevalent type of KS in countries of the Mediterranean basin including Egypt. Several in vitro studies have detected c-kit expression in AIDS related-KS however, only a few studies addressed this issue in the classic type with no data on the ethnicity of studied cases. The prospect of installing targeted anti- c-kit treatment to KS patients presents a promising avenue in KS therapeutics. AIM: To elucidate the expression of c-kit in classic KS cases and study possible relations with expression of HHV8 latency-associated nuclear antigen-1 (LANA-1) and other clinicopathological parameters. METHODS: Twenty four cases of classic KS of the plaque and nodular stages in the lower limb were studied. Immunohistochemical detection of HHV8-LANA-1 and c-kit was carried out on archival paraffin embedded tissue, possession of the Pathology and Dermatology Departments, Alexandria School Of Medicine, Egypt. Statistical analysis of possible relations between both antigens and clinicopathological parameters (patient's age and gender and histological stage) was performed. RESULTS: HHV8 expression was detected in 100% of cases while c-kit immunoreactivity was found in 54.2% of cases. There was no correlation between c-kit and HHV8 immunoreactivity or any of the studied clinicopathological parameters. CONCLUSIONS: This is the first report of c-kit expression in classic KS in an ethnically homogeneous cohort of Arabs of the Mediterranean region. We detected c-kit expression in about half the cases with no relationship to HHV8 LANA expression or clinicopathological parameters.