<i>HNF1B</i>, <i>TSPAN8</i> and <i>NOTCH2</i> gene polymorphisms in women with gestational diabetes

<p><b>Purpose:</b> To investigate genes involved in pancreatic beta cell function, insulin production and glucose metabolism that may predispose to gestational diabetes mellitus (GDM).</p> <p><b>Methods:</b> The study group consisted of 204 women with GDM and 207 women with normal glucose tolerance (NGT). The following polymorphisms were genotyped for each patient: <i>HNF1B</i> rs4430796, <i>TSPAN8</i> rs7961581 and <i>NOTCH2</i> rs10923931. A <i>p</i> value of <.05 was considered to indicate a statistically significant result.</p> <p><b>Results:</b> There was a statistically significant increase in the frequency of HNF1B rs4430796 G allele among pregnant women with GDM (GG+AG versus AA, OR: 1.55, 95% CI: 1.01–2.36, <i>p</i> = .042; G versus A, OR: 1.39, 95% CI: 1.06–1.83, <i>p</i> = .018), whereas there were no statistically significant differences in the distributions of <i>TSPAN8</i> rs7961581 and <i>NOTCH2</i> rs10923931 genotypes and alleles between women with GDM and healthy pregnant women. In the multivariate logistic regression analysis, older age, higher BMI before pregnancy and a higher number of <i>HNF1B</i> rs4430796 G alleles were independent significant predictors of a higher risk of GDM.</p> <p><b>Conclusions:</b> The results of this study suggest that the <i>HNF1B</i> gene rs4430796 G allele may be associated with increased risk of GDM.</p

<i>MTNR1A</i> and <i>MTNR1B</i> gene polymorphisms in women with gestational diabetes

<p>Gestational diabetes mellitus (GDM) is glucose intolerance detected during pregnancy. The <i>MTNR1B</i> gene is the genetic locus associated with type 2 diabetes, that may affect insulin secretion and pancreatic glucose sensing. In this study, we examined the association between <i>MTNR1A</i> (rs2119882) and <i>MTNR1B</i> (rs10830963, rs4753426) gene polymorphisms and the risk of GDM. According to the results of their oral glucose tolerance test (OGTT), the women were divided into two groups: 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). There were no statistically significant differences in the distribution of <i>MTNR1A</i> rs2119882 and <i>MTNR1B</i> rs4753426 genotypes and alleles between women with GDM and healthy pregnant women. With regard to the <i>MTNR1B</i> rs10830963 polymorphism, we observed a statistically significant prevalence of GG and CG genotypes and the G allele among pregnant women with GDM (GG + CG vs CC, OR 1.50, 95% CI 1.02–2.22, <i>p</i> = 0.04; G vs C, OR 1.43, 95% CI 1.07–1.90, <i>p</i> = 0.016). In a multivariate logistic regression analysis, a higher number of <i>MTNR1B</i> rs10830963 G alleles was an independent significant predictor of a higher risk of GDM. The results of our study indicate that <i>MTNR1B</i> rs10830963 polymorphism is associated with GDM susceptibility, and women with a higher number of G alleles have an increased risk of GDM development.</p

Additional file 1: of Picropodophyllin (PPP) is a potent rhabdomyosarcoma growth inhibitor both in vitro and in vivo

Xenotransplanted mice body mass comparison. Average body mass of mice inoculated with RMS cells (controls) and PPP-treated xenotransplanted mice. (PPTX 36 kb

Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis

<div><p>Background</p><p>Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an “angiogenic disease” because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA.</p><p>Objectives</p><p>The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA.</p><p>Methods</p><p>581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA.</p><p>Results</p><p>The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was lower than the number of women with wild type allele -2578A (p = 0.006). Serum VEGF levels were significantly higher in RA patients than in control groups (both p = 0,0001).</p><p>Conclusion</p><p>Present findings indicated that VEGF genetic polymorphism as well as VEGF protein levels may be associated with the susceptibility to RA in the Polish population.</p></div

Correlation of FLT-1 protein concentration of the various clinical parameters (RA).

<p>Correlation of FLT-1 protein concentration of the various clinical parameters (RA).</p

Distribution of genotypes and allele frequencies of <i>FLT-1</i> SNPs among patients with RA and healthy subjects (p = RA vs controls).

<p>Distribution of genotypes and allele frequencies of <i>FLT-1</i> SNPs among patients with RA and healthy subjects (p = RA vs controls).</p

<i>FLT-1</i> gene polymorphisms and protein expression profile in rheumatoid arthritis

<div><p>Objectives</p><p>Inflammation and angiogenesis are a significant element of pathogenesis in rheumatoid arthritis (RA). The FLT-1- triggering factor for production of proinflammatory cytokines-might contributes to inflammation in patients with RA. Association of the <i>FLT-1</i> polymorphisms with different “angiogenic diseases” suggests that it may be a novel genetic risk factor also for RA. The aim of the study was to identify <i>FLT-1</i> genetic variants and their possible association with sFLT-1 levels, susceptibility to and severity of RA.</p><p>Methods</p><p>The <i>FLT-1</i> gene polymorphisms were genotyped for 471 RA patients and 684 healthy individuals. Correlation analysis was performed with clinical parameters, cardiovascular disease (CVD) and anti-citrullinated peptide/protein antibody (ACPA) presence. The sFLT-1 serum levels were evaluated.</p><p>Results</p><p>The <i>FLT-1</i> gene polymorphisms showed no significant differences in the proportion of cases and controls. Furthermore, the <i>FLT-1</i> rs2296188 T/C polymorphism was associated with ACPA-positive RA. Overall, rs9943922 T/C and rs2296283 G/A are in almost completed linkage disequilibrium (LD) with D’ = 0.97 and r2 = 0.83. The <i>FLT-1</i> rs7324510 A allele has shown association with VAS score (p = 0.035), DAS-28 score (p = 0.013) and ExRA presence (p = 0.027). Moreover, other clinical parameters were also higher in RA patients with this allele. In addition, <i>FLT-1</i> genetic variants conferred higher sFLT-1 levels in RA patients compared to controls.</p><p>Conclusion</p><p><i>FLT-1</i> rs7324510 C/A variant may be a new genetic risk factor for severity of RA. Examined factor highly predispose to more severe disease activity as well as higher sFLT-1 levels in RA.</p></div

Demographic and clinical characteristics of the RA patients with CVD and without CVD.

<p>Demographic and clinical characteristics of the RA patients with CVD and without CVD.</p

Distribution of genotypes and allele frequencies of VEGF SNPs among Polish patients with RA and healthy subjects.

<p>OR adjusted for sex and age.</p

Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis - Fig 3

<p>Variation in VEGF expression levels in RA patients and control group in relation to: <b>A)</b>—1154 A/G (rs1570360) VEGF genotypes; <b>B)</b>—2578 A/C (rs699947) VEGF genotypes; <b>C)</b>—634 G/C (rs2010963) VEGF genotypes.</p