Biomedical subjects

G Matullo

Publications and source records attributed to G Matullo.

26 records · Page 2Linked to original sources

PubMed2000

Acute myocardial infarction in young adults: prognostic role of angiotensin-converting enzyme, angiotensin II type I receptor, apolipoprotein E, endothelial constitutive nitric oxide synthase, and glycoprotein IIIa genetic polymorphisms at medium-term follow-up.

BACKGROUND: A number of reports have investigated the association between various gene polymorphisms and the phenotypic expression of myocardial infarction. No investigations have evaluated the prognostic role of genetic factors in young people with premature coronary disease. The aim of this study was to investigate the influence of genetic factors compared with that of conventional risk factors on follow-up events in a population of Italian young adults with myocardial infarction. METHODS AND RESULTS: The study population consisted of 106 young patients (mean age 40 +/- 4 years, range 23 to 45 years) with diagnosis of acute myocardial infarction. Clinical and genetic data from the group of patients with events during follow-up were compared with those from patients without events. The following genetic polymorphisms were tested: angiotensin I converting enzyme, angiotensin II type I receptor, apolipoprotein E (ApoE), endothelial constitutive nitric oxide synthase, and platelet glycoprotein IIIa. Coronary angiography was performed in 94 patients. Coronary angiography showed coronary artery disease in 93% of patients. During follow-up (46 +/- 12 months, range 25 to 72) the overall combined end points (cardiac death, myocardial infarction, and revascularization procedures) accounted for 21 events. Family history of coronary artery disease, smoking, stenosis of the left anterior descending artery at coronary angiography, and ApoE polymorphism (presence of epsilon4 allele) were significantly more prevalent (univariate analysis) in the group of patients with events. Logistic multivariate analysis showed that ApoE polymorphism (P =. 004, odds ratio [OR] 6.8, 95% confidence interval [CI] 2 to 22), family history (P =.005, OR 8.3, 95% CI 2 to 35), smoking after acute myocardial infarction (P =.008, OR 10.9, 95% CI 2 to 62), and left anterior descending coronary artery disease (P =.02. OR 6.6, 95% CI 1.3 to 33) were independent predictors of adverse events. CONCLUSIONS: Myocardial infarction at a young age is commonly characterized by evidence of multiple cardiovascular risk factors and by a favorable prognosis in short- and medium-term follow-up. Evidence of significant disease at coronary angiography suggests the presence of a premature atherosclerotic process. ApoE polymorphism (presence of epsilon4 allele) appears to be a strong independent predictor of adverse events, suggesting a remarkable influence in the accelerated coronary disease.

Adult↗

PubMed1998

Plasma activity and insertion/deletion polymorphism of angiotensin I-converting enzyme: a major risk factor and a marker of risk for coronary stent restenosis.

BACKGROUND: Tissue proliferation is almost invariably observed in recurrent lesions within stents, and ACE, a factor of smooth muscle cell proliferation, may play an important role. Plasma ACE level is largely controlled by the insertion/deletion (I/D) polymorphism of the enzyme gene. The association among restenosis within coronary stents, plasma ACE level, and the I/D polymorphism is analyzed in the present prospective study. METHODS AND RESULTS: One hundred seventy-six consecutive patients with successful, high-pressure, elective stenting of de novo lesions in the native coronary vessels were considered. At follow-up angiography, recurrence was observed in 35 patients (19.9%). Baseline clinical and demographic variables, plasma glucose and serum fibrinogen levels, lipid profile, descriptive and quantitative angiographic data, and procedural variables were not significantly different in patients with and without restenosis; mean plasma ACE levels (+/-SEM) were 40.8+/-3.5 and 20.7+/-1.0 U/L, respectively (P<.0001). Diameter stenosis percentage and minimum luminal diameter at 6 months showed statistically significant correlation with plasma ACE level (r=.352 and -.387, respectively P<.001). Twenty-one of 62 patients (33.9%) with D/D genotype, 13 of 80 (16.3%) with I/D genotype, and 1 of 34 (2.9%) with I/I genotype showed recurrence; the restenosis rate for each genotype is consistent with a codominant expression of the allele D. CONCLUSIONS: In a selected cohort of patients, both the D/D genotype of the ACE gene, and high plasma activity of the enzyme are significantly associated with in-stent restenosis. Continued study with clinically different subsets of patients and various stent designs is warranted.

Adult↗

PubMed1997

Seventy-five nuclear DNA polymorphisms in an Italian sample: a comparative worldwide study.

A well defined Italian sample from Trino Vercellese (Northern Italy) is analysed for 75 nuclear DNA RFLPs. It represents the only European sample [Matullo et al 1994] which is unmixed in a comparative study of eight populations from four continents [Bowcock et al 1991a; Lin et al 1994]. Genetic substructure of this sample has been investigated by allele sharing distances and no bias or higher homogeneity is shown. Genetic variability between populations was measured by the FST statistics (average FST was 0.138 +/- 0.086). Average heterozygosity for eight populations was 0.312 +/- 0.069. Genetic distances were evaluated between pairs of populations. Phylogenetic trees were reconstructed and principal component analysis performed. Particular attention has been given to the genetic relationship between our sample and the mixed-Caucasoid sample: 14 out of 75 markers show statistically significant frequency differences (P < 0.05), 5 of which are significant at a probability level < 1%: GH/Bg1II (Lower system), D7S1/HindIII, D17S71/MspI, EPB3/PstI, HLA-DQA. Hypotheses on admixed origin of Europeans has been discussed.

Biological Evolution↗

PubMed1995

Restriction of the T-cell receptor V delta gene repertoire is due to preferential rearrangement and is independent of antigen selection.

To determine whether the limited V gene usage by the T-cell receptor delta (TCRD) chain is dictated by preferential rearrangement or by antigen selection, we characterized and compared the TCRDV gene repertoire of the productive with that of the unproductive allele in 80 human TCRG/TCRD clones. Six different V genes were found on the expressed allele; two of them, provisionally named DV7 and DV8, have not been described before on the surface of TCRG/TCRD T cells. Overall, six V genes and six non-V elements were isolated from the unproductive allele. Interestingly, the same set of genes was rearranged both in the productive and in the unproductive chromosome. These findings seem to suggest that antigen-independent mechanisms play a major role in the restriction of the TCRDV gene repertoire.

Alleles↗

PubMed1995

Analysis of HLA-A, C, B, DR and DQ loci in an Italian sample of possible Celtic origin.

Trino Vercellese, a village of Piedmont (Italy), was selected with the aim at reconstructing the genetic history of a putative Celtic sample known to be settled in Italy with the name of Rigomagus since pre-roman times. The HLA-A, Cw, B, DR and DQ antigens of 101 unrelated individuals have been typed. The antigens characterizing this sample for their higher frequency are shown to be A3, A11, A32, B35, B39, Bw52, Cw4, DRw11, DRw13, DQw7. Gene frequencies are estimated by maximum likelihood and Hardy-Weinberg equilibrium was tested with no deviant genetic locus. Two-locus haplotype frequencies were also estimated and those with significant associations tabulated. "Extended" haplotypes were reconstructed: the three most frequent haplotypes (covering a total frequency of 11.5%) share the same Cw, B, DR and DQ alleles. Comparisons with other Italian and European samples are indicated to challenge archeological evidence of a pre-roman genetic stratification of the people living in our old Rigomagus.

Alleles↗

PubMed1994

T cell receptor V delta 2-C alpha transcripts are present in the thymus but virtually absent in the periphery.

To investigate whether the V delta 2-(D)-J alpha gene configuration, characteristically associated with the major subset of acute lymphoblastic leukemias in humans, might have a physiologic role in T cell ontogeny, we have looked for V delta 2-C alpha transcripts in the thymus and peripheral blood of normal donors. Here we show by PCR analysis that these transcripts are virtually absent in the PBMC, whereas they are present in fetal and postnatal thymus. Interestingly, over 80% of 43 V delta 2-C alpha cDNAs randomly isolated from one postnatal thymus appeared to maintain an open reading frame. This suggests that in the thymus the V delta 2-C alpha products might be exposed to selective pressure. Furthermore, in two of three thymuses tested for J alpha usage, it was found overrepresented in a J alpha element (J alpha 58) located 2 kb downstream to a pseudo-J (J alpha 61), known to be a hot spot of recombination in alpha beta committed cells. A possible alternative pathway to alpha beta T cell differentiation via a V delta 2-J alpha intermediate is discussed.

Alternative Splicing↗

PubMed1994

RFLP analysis on a sample from northern Italy.

We analysed a sample of 55 unrelated individuals from Trino Vercellese, a village in northern Italy. It represents the only European sample which is unmixed in a comparative study of eight populations from four continents [Bowcock et al 1991a; Lin et al 1994]. RFLP analysis was performed on 32 DNA markers, for a total of 37 independent alleles. Genetic variability between populations was measured by the FST statistics (average FST is 0.138). Average heterozygosity was calculated for each marker and for each population. Genetic distances were evaluated between pairs of populations. Phylogenetic trees were reconstructed and principal component analysis performed.

Alleles↗

PubMed1990

High prevalence of T-cell receptor V delta 2-(D)-D delta 3 or D delta 1/2-D delta 3 rearrangements in B-precursor acute lymphoblastic leukemias.

Rearrangement of the immunoglobulin (Ig) and T-cell receptor (TcR) genes generally has been considered a useful marker of B- and T-cell lineage in lymphoproliferative disorders. However, concomitant rearrangements of Ig and TcR genes have been commonly reported in the most immature lymphoid malignancies, mainly in B-cell precursor acute lymphoblastic leukemia (ALL). To better characterize the nature of this lineage promiscuity, we have analyzed the configuration of the TcR delta locus in 75 B-precursor ALL. The large majority of cases (87%) displayed a rearrangement or deletion at the delta locus. Among the 57 nondeletional rearrangements, two patterns were predominant and both appeared to derive from partial joining: a V delta-(D)-D delta 3 (32/57) and a D delta 1/2-D delta 3 (11/57) type. A single V delta gene (V delta 2) appeared to be involved in the first type of rearrangement. These findings are at variance with T-ALL, where rearrangements 5' to V delta 2 are usually found. It remains to be elucidated whether this incomplete attempt of V delta 2 gene assembly is related to the neoplastic event or represents a physiologic predisposition occurring during early stages of the normal lymphocyte differentiation.

B-Lymphocytes↗