Variation in the calpain-10 gene is not associated with gestational diabetes mellitus.

BACKGROUND: In several large studies an association between certain single-nucleotide polymorphisms (SNP) of the calpain-10 gene (CAPN10) with type 2 diabetes mellitus (T2D) has been identified. Since T2D and gestational diabetes mellitus (GDM) seem to be linked pathophysiologically, we examined the frequencies of CAPN10-polymorphisms in women with GDM. METHODS: By using real-time PCR assisted melting curve analysis samples of 204 women with GDM and 297 controls were tested for variations of SNP-43, -44, -63 and Indel-19 of CAPN10. RESULTS: Since the genotype frequencies found in SNP-44 among the controls did not meet the Hardy-Weinberg-Equilibrium, the further analysis was performed with SNP-43, -63 and Indel-19 only. Herein, the distribution of neither genotype nor allele nor haplogenotype-combination nor haplotype showed a significant difference between both groups. CONCLUSIONS: Variations of SNP-43, -63 and Indel-19 of CAPN10 were not associated with an increased risk of developing GDM.

Osteopontin is a hematopoietic stem cell niche component that negatively regulates stem cell pool size.

Stem cells reside in a specialized niche that regulates their abundance and fate. Components of the niche have generally been defined in terms of cells and signaling pathways. We define a role for a matrix glycoprotein, osteopontin (OPN), as a constraining factor on hematopoietic stem cells within the bone marrow microenvironment. Osteoblasts that participate in the niche produce varying amounts of OPN in response to stimulation. Using studies that combine OPN-deficient mice and exogenous OPN, we demonstrate that OPN modifies primitive hematopoietic cell number and function in a stem cell-nonautonomous manner. The OPN-null microenvironment was sufficient to increase the number of stem cells associated with increased stromal Jagged1 and Angiopoietin-1 expression and reduced primitive hematopoietic cell apoptosis. The activation of the stem cell microenvironment with parathyroid hormone induced a superphysiologic increase in stem cells in the absence of OPN. Therefore, OPN is a negative regulatory element of the stem cell niche that limits the size of the stem cell pool and may provide a mechanism for restricting excess stem cell expansion under conditions of niche stimulation.

Loss of imprinting of the insulin-like growth factor 2 and the H19 gene in testicular seminomas detected by real-time PCR approach.

IGF2 and H19 are imprinted genes in normal human tissue, but many studies have observed a loss of imprinting (LOI) of these genes in tumors as an epigenetic alteration of the DNA, that leads to a biallelic expression predisposing cells to carcinogenesis and tumor growth. The aim of this study was to test the reliability of LightCycler-assisted Real-time PCR in detecting LOI of IGF2 and H19 in 39 patients with testicular germ cell tumors by comparing these results with the analysis generated by the golden standard restriction fragment length polymorphism (RFLP). With LightCycler-assisted Real-time PCR for IGF2 44% and for H19 49% of the patients were found to be heterozygous. This was consistent with the results obtained by RFLP, but surprisingly RFLP failed in more than 7% of the patients. In detecting LOI (for IGF2 in 41% and for H19 in 68% of the informative patients) the approach by RFLP was superior, since the results derived from LightCycler-assisted Real-time PCR showed reliable results in 76 and 10% of the samples concerning IGF2 and H19, respectively. Again, no discrepancy between the results obtained by the two methods occurred. In sum, LightCycler-assisted Real-time PCR is a sufficiently working approach for the rapid and reliable detection of heterozygosity of IGF2 or H19 gene and identification of LOI of IGF2 and thus may be helpful in conducting large epidemiological studies. However, for the identification of LOI of the H19 gene in this cohort it possesses only restrictive use.