Biomedical subjects

Sabrina Ballerini

Publications and source records attributed to Sabrina Ballerini.

5 recordsLinked to original sources

PubMed2005

Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele.

BACKGROUND: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD). METHODS: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler. RESULTS: We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P < 0.05], but no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE epsilon4 allelic variants were at increased risk of LOAD (OR = 19.98; P < 0.0001). CONCLUSION: The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE epsilon4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to beta-amyloid-mediated neurodegeneration.

Age of Onset↗

PubMed2005

Post-transcriptional regulation of Smad7 in the gut of patients with inflammatory bowel disease.

BACKGROUND & AIMS: Transforming growth factor (TGF)-beta1 is one of the most powerful endogenous negative regulators of inflammation. In patients with inflammatory bowel disease, despite abundant local TGF-beta1, there is a failure of TGF-beta-mediated negative regulation of nuclear factor kappaB activation and proinflammatory cytokine production because of increased intracellular expression of the endogenous inhibitor of TGF-beta1 signaling, Smad7. In this study, we examined the molecular mechanism underlying the induction of Smad7 in the human gut. METHODS: Whole intestinal mucosal and lamina propria mononuclear cell samples were analyzed for Smad7 by real-time polymerase chain reaction and Western blotting. Smad7 ubiquitination and acetylation, and interaction of Smad7 with the intrinsic histone acetyltransferase, p300, were examined by immunoprecipitation and Western blotting. The effect of p300 silencing on Smad7 expression was determined in Crohn's disease lamina propria mononuclear cells. RESULTS: We showed that Smad7 is not transcriptionally regulated in human gut but that its increase in patients with inflammatory bowel disease is due to posttranscriptional acetylation and stabilization by p300, which prevents Smad7 ubiquitination and degradation in the proteasome. Hence, Smad7 protein in cells from normal gut is ubiquitinated and rapidly degraded. In contrast, in inflamed gut, Smad7 is acetylated and not ubiquitinated, is not degraded, and can be decreased by short interfering RNA to p300. CONCLUSIONS: These results identify posttranslational protein modification as of importance in chronic gut inflammation in humans.

Acetylation↗

PubMed2004

Hypermethylation of the CpG islands in the promoter region of the GSTP1 gene in prostate cancer: a useful diagnostic and prognostic marker?

BACKGROUND: Recently, many studies have focused on the potential diagnostic value of the promoter hypermethylation of the GSTP1 gene in prostate cancer. METHOD: A total of 144 patients, undergoing eight-core prostatic biopsies for a clinically suspected prostate cancer, was analyzed. Two different tissue samples were collected from the same area of the prostate and then divided for both genomic DNA extraction and pathological examination. In order to perform molecular analysis, prostatic tissue samples were digested with the methylation-sensitive restriction enzyme HpaII and then amplified by conventional polymerase chain reaction (PCR). RESULTS: Prostate cancer was diagnosed in 42/144 patients, and promoter hypermethylation of GSTP1 gene was detected in 31/42 of prostate cancer (sensitivity=74%) and in 2/102 of negative specimens (specificity=98%). A significant association between GSTP1 promoter hypermethylation both with a Gleason score >or=7 (Fisher's exact P=0.01) and the presence of Gleason grade 4 and/or grade 5 (Fisher's exact P=0.03) was found. CONCLUSION: Promoter hypermethylation of the GSTP1 gene is a highly specific--but not a very sensitive--marker of prostate cancer. Our data showed a significant association between the methylation status of the GSTP1 gene and Gleason score and grade, suggesting a potential prognostic value of this epigenetic DNA alteration.

Aged↗

PubMed2003

Analysis of GSTP1-1 polymorphism using real-time polymerase chain reaction.

BACKGROUND: Glutathione transferases (GSTs) play an important role in the protection of cells from the products of oxidative stress as well as from several environmental carcinogens. The GSTP1-1 gene class is significantly overexpressed in many human tumors. Four allelic variants have been described for the GSTP1-1 gene (*A, *B, *C, *D) leading to different amino acid substitutions in position 105 and 114 of the protein sequence. The proteins encoded by the different alleles show different abilities to metabolize carcinogens and anticancer agents, suggesting an association between GSTP1 polymorphism and the risk for a variety of cancers as well as between said polymorphism and varying responses to cancer treatments. METHODS: The GSTP1-1 polymorphism was determined using a real-time polymerase chain reaction (PCR) and fluorescence resonance energy transfer with a Light-Cycler Instrument. ARMS was used in the case of *A/*C or *B/*D heterozygosity. We used this method to determine the GSTP1-1 polymorphism in 250 free-living Italian subjects of both sexes. RESULTS: Among 250 subjects representative of an Italian population, we observed the following allelic frequencies: f(A)=0.710, f(B)=0.236, f(C)=0.054 and f(D)=0. The observed phenotypes are in Hardy-Weinberg equilibrium (chi(2)=0.71, df=4, P=0.95). CONCLUSIONS: We have extended and improved a method of GSTP1-1 complete genotyping. This method provides the ability to genotype 30 samples in 2 h and it represents a fast, reliable and automated methodology to determine GSTP1-1 polymorphism in order to perform large-scale population studies.

Adult↗

PubMed2002

Apolipoprotein E genotyping: a comparative study between restriction endonuclease mapping and allelic discrimination with the LightCycler.

BACKGROUND: The apolipoprotein E (apo E) polymorphism is associated with the risk of developing cardiovascular disease and the risk and the time of onset of Alzheimer's disease. Therefore, the interest in apo E genotyping is high, both for epidemiological research and for the purpose of diagnosing dyslipidemia or dementia. The aim of our study was to compare and evaluate two different methods for apo E genotyping, both on the basis of polymerase chain reaction (PCR). METHODS: Genomic DNA of 197 subjects was extracted from whole blood. The first method involved DNA amplification performing a PCR using specific primers and endonuclease restriction mapping. The second one was a DNA assay that used real-time PCR on the LightCycler instrument (Roche). RESULTS: We obtained a 100% concordance between the two methods and we found a relative allelic frequency distribution typical for an Italian population. CONCLUSIONS: The LightCycler (LC) allelic discrimination method for apo E genotyping seems to be rapid, simple and accurate, suggesting a possible successful use of this method for diagnostic purposes.

Alleles↗