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Giuseppe Matullo

Publications and source records attributed to Giuseppe Matullo.

23 records · Page 2Linked to original sources
PubMed2003

Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study.

Inherited single nucleotide polymorphisms (SNPs) of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. We investigated the role of SNPs in three DNA repair genes (X-ray repair cross-complementing group 1-Arg399Gln, exon 10; X-ray repair cross-complementing group 3-Thr241Met, exon 7; and xeroderma pigmentosum-D-Lys751Gln, exon 23) and their combination, in modulating the levels of "bulky" DNA adducts in a population sample of 628 Italian healthy individuals belonging to the prospective European project "European Prospective Investigation into Cancer and Nutrition." DNA-adduct levels were measured as relative adduct level per 10(9) nucleotides by (32)P-post DNA labeling assay in WBCs from peripheral blood. Genotyping was performed by PCR-RFLP analysis or primer extension/denaturing high-performance liquid chromatography technique. We found a dose-response relationship between the number of at-risk alleles and levels of adducts (P = 0.0046). Individuals with at least three variant alleles had a statistically significant odds ratio (OR) for being in the highest tertile of adducts compared with those with undetectable adducts [three alleles, adjusted OR = 5.07, 95% confidence interval (CI) = 1.29-19.9; four alleles, adjusted OR = 5.03, 95% CI = 1.18-21.45; five alleles, adjusted OR = 7.65, 95% CI = 0.94-62.2]. Our study suggests that the combined effect of multiple variant alleles may be more important than the investigation of single SNP in modulating DNA repair capacity.

Alleles↗
PubMed2002

Haptoglobin phenotype and the risk of restenosis after coronary artery stent implantation.

We recently demonstrated that an allelic polymorphism in the haptoglobin gene is a major determinant of susceptibility to a number of vascular disorders. We set out to determine if haptoglobin phenotype was predictive of the development of restenosis in a consecutive series of patients, all of whom underwent stent implantation followed by repeat angiography with quantitative coronary angiography analysis 6 months later. This study included 214 consecutive patients undergoing stent implantation for de novo lesions between 1998 and 1999 in Aalst, Belgium. All underwent follow-up quantitative coronary angiography analysis 6 months after the procedure. The haptoglobin phenotype was determined by electrophoresis. No significant differences were found between patients segregated by phenotype with respect to clinical, procedural, and angiographic factors previously suggested to influence the development of restenosis. None of the diabetic patients homozygous for the haptoglobin 1 allele developed restenosis compared with a >50% restenosis rate for diabetic patients with at least 1 haptoglobin 2 allele (p <0.02). In all patients (diabetic and nondiabetic), we observed a trend toward a lower incidence of restenosis in patients homozygous for the 1 allele (21% vs 33%, p <0.09). Moreover, we found a graded risk relation to the number of haptoglobin 2 alleles. The risk of developing restenosis was greater in subjects with 2 haptoglobin 2 alleles (36%) than in those with 1 haptoglobin 2 allele (31%) or no haptoglobin 2 alleles (21%). Thus, knowledge of the haptoglobin phenotype may be useful in assessing and utilizing new therapies that attempt to reduce restenosis, and may have important implications for the risk stratification algorithm used in managing diabetic patients with coronary artery disease.

Aged↗
PubMedDate not supplied

Intracoronary beta-irradiation prevents excessive in-stent neointimal proliferation in de novo lesions of patients with high plasma ACE levels. The BetAce randomized trial.

BACKGROUND: This study evaluated vascular brachytherapy (VBT) as a potent antiproliferative treatment to prevent in-stent restenosis (ISR) after coronary angioplasty of de novo lesions in patients carrying the D allele of the I/D polymorphism of the ACE gene and high ACE plasma levels (>34 U/l). METHODS AND MATERIALS: A prospective randomized trial was designed to detect a 30% improvement in the minimal lumen diameter (MLD) of the stenotic artery, as measured by quantitative coronary analysis (QCA), 6 months following VBT at the time of stented angioplasty. All patients were carriers of the D allele of the ACE gene, with plasma ACE levels >34 U/l. RESULTS: Thirty-one patients (33 stenoses) were allocated to stent implantation (control group) and 30 patients (31 stenoses) to VBT and stented angioplasty. After angioplasty, in-stent MLD was similar in the two groups. At 6 months in the control group, in-stent MLD had decreased to 1.74+/-0.8 versus 2.25+/-1.05 mm in the VBT group (P=.04). The mean in-stent diameter was 2.3+/-0.8 mm in the control group versus 2.9+/-1.05 mm after VBT (P=.02), and the restenosis rate was 37.5% versus 17.9%, respectively (P=.08). At 6 months, a higher need for target vessel revascularization (TVR) was observed in the control group: 35.5% versus 13.3% (P=.04). CONCLUSIONS: This randomized study confirms that patients with high plasma ACE concentrations are exposed to an increased risk for ISR after coronary stenting. The preventive use of VBT in these patients reduced neointimal formation by 65% such that the MLD at follow-up was increased by 29% compared with the control group.

Alleles↗
PubMedDate not supplied

Association between transforming growth factor beta1 gene polymorphisms and IgA nephropathy.

BACKGROUND: Transforming growth factor beta1 (TGF-beta1) plays an important role in the modulation of cellular growth and differentiation in a wide variety of cell types and in the production/degradation of the extracellular matrix (ECM). We investigated whether G-800A, C-509T and Leu10-->Pro polymorphisms in the TGF-beta1 gene could be involved in the development and progression of immunoglobulin A nephropathy (IgAN). METHODS: DNA samples were obtained from 101 patients with biopsy proven IgA mesangial nephropathy and 118 healthy controls. The genotypes of G-800A, C-509T and Leu10-->Pro polymorphisms in the TGF-beta1 gene were determined by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) with MaeIII, Eco 81I and Pst I, respectively. RESULTS: No significant differences were observed in the genotype distribution of the three TGF-beta1 polymorphisms between patients and controls. The TAC haplotype (T=Leu10, A-800 and C-509 alleles, respectively) was significantly associated with IgAN (p=0.043; odds ratio (OR) =2.334, 95 % confidence interval (95%CI) 1.01-5.41). CONCLUSION: Our study suggests that the haplotype reconstruction of TGF-beta1 gene polymorphisms could be more informative than the investigation of single nucleotide polymorphisms for defining the associated risk of developing IgAN. Further research is needed on larger cohorts to confirm TGF-beta1 involvement and test other TGF-beta1 variants with possible additive or synergistic effects.

Adenine↗