The Estimation of GC Repeats in Promoter P1 of IGF-1 Gene and Their Influence on IGF-1 Plasma Levels in Stable Angina Patients

Increased plasma levels of insulin-like growth factor 1 (IGF-1) are observed in advanced arteriosclerosis, but the reasons for these elevated levels remain unknown. One possibility to explain them is variation in the sequences that control IGF-1 gene expression. The goal of this study was to determine the effect of molecular variants of the IGF-1 P1 promoter on IGF-1 serum levels and to determine the impact of IGF-1 levels on the severity of coronary atherosclerosis. Methods: Blood samples were collected from 101 consecutive patients undergoing routine angiography. Genomic DNA was isolated from the nucleated cells of the blood plasma as described (2). Based on the presence of conformational differences in the DNA strand and on the absence of single nucleotide polymorphisms, the DNA from 38 patients was further analyzed by the “allelic ladder” method to determine the number of repeated GC dinucleotides in the P1 promoter of the IGF-1 gene. In addition, we analyzed serum growth hormone levels in order to examine the effect on systemic IGF-1 synthesis. Results: Conformational differences in the P1 promoter of the IGF-1 gene were observed in 38 out of the 101 patients. Several genotypes, depending on the number of GC repeats, were observed (11/19,17/19,18/19,18/21,19/19,19/20,19/21). Interestingly, a family history of coronary artery disease was seen less often among individuals heterozygous for the GC repeats. A lower IGF-1 levels were seen in non-variant carriers (homozygous genotypes for 19 or 21 repeats of GC, or heterozygous genotype 19/21) when compared to the variant group (other heterozygous genotypes then 19/21) (181.6 ± 47.9 ng/mL vs. 227.7 ± 73.7, p = 0.026). A correlation between IGF-1, IGF-binding protein number 3, and growth hormone levels (p = ns) was not observed, and there were no significant differences in the growth hormone levels in the studied group of patients (p = ns)

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Zinc transporter gene expression is regulated by pro-inflammatory cytokines: a potential role for zinc transporters in beta-cell apoptosis?

<p>Abstract</p> <p>Background</p> <p>β-cells are extremely rich in zinc and zinc homeostasis is regulated by zinc transporter proteins. β-cells are sensitive to cytokines, interleukin-1β (IL-1β) has been associated with β-cell dysfunction and -death in both type 1 and type 2 diabetes. This study explores the regulation of zinc transporters following cytokine exposure.</p> <p>Methods</p> <p>The effects of cytokines IL-1β, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) on zinc transporter gene expression were measured in INS-1-cells and rat pancreatic islets. Being the more sensitive transporter, we further explored ZnT8 (Slc30A8): the effect of ZnT8 over expression on cytokine induced apoptosis was investigated as well as expression of the insulin gene and two apoptosis associated genes, BAX and BCL2.</p> <p>Results</p> <p>Our results showed a dynamic response of genes responsible for β-cell zinc homeostasis to cytokines: IL-1β down regulated a number of zinc-transporters, most strikingly ZnT8 in both islets and INS-1 cells. The effect was even more pronounced when mixing the cytokines. TNF-α had little effect on zinc transporter expression. IFN-γ down regulated a number of zinc transporters. Insulin expression was down regulated by all cytokines. ZnT8 over expressing cells were more sensitive to IL-1β induced apoptosis whereas no differences were observed with IFN-γ, TNF-α, or a mixture of cytokines.</p> <p>Conclusion</p> <p>The zinc transporting system in β-cells is influenced by the exposure to cytokines. Particularly ZnT8, which has been associated with the development of diabetes, seems to be cytokine sensitive.</p