Polymorphisms and haplotypes in VDR gene are associated with female idiopathic infertility.

Unexplained infertility refers to the absence of a definable cause of reproductive failure. Vitamin D receptor (VDR) acts as a transcription factor and regulates a number of vitamin D-responsive genes, including those involved in the immune system. Recent finding that VDR is expressed in reproductive tissues suggests a possible importance of vitamin D in pregnancy. We conducted a case-control study to examine the association of polymorphisms in VDR gene with reproductive success. DNA from 117 female patients with unexplained infertility and 130 fertile controls was isolated from peripheral blood and VDR genotypes (FokI, BsmI, ApaI and TaqI) were detected by PCR-RFLP. Haplotypes were determined using Haploview software. Our results show significant association of FokI and BsmI polymorphisms with infertility (p < 0.05). The haplotype analysis confirmed strong linkage disequilibrium between closely positioned BsmI, ApaI and TaqI polymorphisms. Two haplotypes were associated with infertility: (i) haplotype bAT was increasing the risk for secondary infertility; while (ii) haplotype BAT had a protective role against primary infertility (p < 0.05). By changing the expression and the activity of VDR gene, which leads to the change in expression of vitamin D-responsive genes, these polymorphisms and haplotypes could possibly have an effect on immune system in the female reproductive tract.

Genetics of suspected thrombophilia in Serbian females with infertility, including three cases, homozygous for FII 20210A or FV 1691A mutations.

Reproductive failure (recurrent foetal loss, unexplained infertility and IVF implantation failure) may be, in a number of cases, explained by thrombophilia, either acquired or inherited. Several genes contribute to thrombophilia, some with major effect (Factor V, Factor II), and some with minor effect (MTHFR, PAI-1, ATIII, etc.). The aim of this study was to estimate frequency of thrombophilia-associated genotypes (FII20210G > A, FV1691G > A, MTHFR677C > T and PAI-1 -675 4G/5G) in a group of 1631 Serbian women experiencing reproductive failure, and compare it with a healthy, female control group. Our results showed marginally significant (p = 0.050) differences in allele frequencies between patients and controls for the FV1691 mutations. For the FII20210G > A, although the statistical significance was not achieved (p = 0.076), we found higher frequency of variant allele in patients compared to controls (1.87% vs. 0.38%, respectively) which may point to a possible role of this polymorphism in thrombotic events. For the MTHFR677C > T and PAI-1 -675 4G/5G, we found no difference in distributions of genotype or allele frequencies between these two groups (p > 0.05). For three subjects with very rare genotypes (two patients homozygous for FV1691G > A and one patient homozygous for FII20210G > A) we performed additional biochemical analyses for haemostasis, as well as genotyping of two polymorphisms (MTHFR1298A > C and ATIII786G > A).

[Gigantic ovarian and suprarenal cysts ten years after enucleation of unilateral retinoblastoma].

INTRODUCTION: Retinoblastoma (RB) is the most common eye tumour in children and is curable. Patients with hereditary RB have increased risk of developing additional tumours, predominantly sarcomas. The published results on the treatment of bilateral RB have shown that 10-15% of patients develop second primary tumours (SPT). Average latent period, e.g. the period from the diagnosis of bilateral RB to the appearance of SPT is 10.4 years. In the literature, the appearance of second benign tumours in patients suffering from unilateral and bilateral RB has not been analyzed separately. However, the size and the location of benign tumours can cause serious complications. CASE OUTLINE: We present a 14-year-old female patient. At age 4 years, her left eye was enucleated owing to unilateral RB. In the postoperative period, she did not undergo irradiation, nor did she receive chemotherapy. On her regular ophthalmologic check-up, the patient informed us that her belly was "swelling" over the past four months. She had no pains or other complaints. The abdomen was significantly above the level of the chest, tense, painless on palpation, with obvious fluctuations. Abdominal echosonography confirmed the presence of a huge multilocular cystic formation, 19 x 18 cm in diameter, spreading from the pelvis to the epigastrium, and pressing the liver and spleen. A cyst of 4.7 cm in diameter was observed in the upper pole of the left kidney. Both the gigantic cyst of the left ovary (weighing 10300 g) and the left suprarenal cyst (weighing 30 g) were removed. CONCLUSION: We report a patient who developed second non-ocular tumours (ovarian and suprarenal cysts) after successful treatment of unilateral RB. Patients treated for RB (hereditary and non-hereditary) should be checked regularly and meticulously. Early recognition of tumours, treatment can prevent possible complications.

Comparison of promoter regions of SOX3, SOX14 and SOX18 orthologs in mammals.

SOX proteins constitute a large family of diverse and well conserved transcription factors implicated in the control of various developmental processes. Previously we have cloned and characterized human SOX3, SOX14 and SOX18 genes and performed functional characterization of their promoter regions. To better understand organization and function of SOX3, SOX14 and SOX18 promoters and to determine evolutionary conserved regulatory regions, we performed comparative genomic analyses of orthologous genes promoters. Mammalian orthologs of the human SOX3, SOX14 and SOX18 genes show high sequence identity in their promoter regions, particularly within basal promoters of the respective human genes. Binding sites for transcription factors NF-Y, Sp1 and USF1, previously shown to play critical roles in transcriptional regulation of these human genes, are highly conserved in sequence and position among diverse mammalian species. Conservation of binding sites might indicate their highly significant roles in maintaining the transcriptional regulation of these genes among different species.

Structural and functional characterization of the human SOX14 promoter.

SOX14 is a member of SOX gene family of putative transcriptional regulators. In this study we described the initial characterization of the human SOX14 gene promoter. The transcription start site was mapped by primer extension analysis. The minimal SOX14 promoter region that confers the basal promoter activity, as well as a proximal enhancer, was determined using promoter-reporter constructs. By mutational analysis we have shown that CCAAT box motif present in the SOX14 promoter plays a functional role in the transcription of this gene.