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R Abbate

Publications and source records attributed to R Abbate.

At least 19 recordsLinked to original sources
PubMed2001

High cysteine levels in renal transplant recipients: relationship with hyperhomocysteinemia and 5,10-MTHFR polymorphism.

BACKGROUND: Long-term survival of renal transplant recipients seems to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. Preliminary data available in the literature found high levels of cysteine (Cy) as a risk factor for deep venous thrombosis independently of high homocysteine (tHcy) levels, but no data are available about Cy levels in renal transplant recipients. METHODS: To investigate Cy, tHcy, and plasminogen activator inhibitor-1 (PAI-1) levels and the prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied 70 stable renal transplant recipients and 66 age- and sex-matched normal subjects as controls. RESULTS: Cy, tHcy, and PAI-1 levels were significantly higher in renal transplant recipients with respect to controls (Cy: 254 micromol/L [117-466] vs. 198 micromol/L [99-331], P<0.001; tHcy: 17.0 micromol/L [4.0-68] vs. 8.1 micromol/L [2.0-24.0], P<0.00001; PAI-1: 16.8 IU/ml [5.1-45.5] vs. 7.9 IU/ml [4.0-18.0], P<0.00001). High Cy levels were detected in 35.8% of patients. Hyperhomocysteinemia, both in the fasting state and postmethionine loading test, was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels within the fourth quartile with respect to the other quartiles were markedly increased in renal transplant recipients even after adjustment for prevalent cardiovascular risk factors, glomerular filtration rate, tHcy and, Cy, respectively (Cy: 29.0 micromol/L [95% CI 7.0-111]; tHcy: 29.9 micromol/L [95% CI 7.5-118.1]). Fasting tHcy levels correlated well with PAI-1 (r=0.65; P<0.0001) but not with Cy levels (r=0.10; P=0.4). The prevalence of the MTHFR 677TT genotype in renal transplant recipients was not significantly higher in patients than in controls (mutant allele frequency: 0.48 in patients and 0.47 in controls) and was associated with significantly higher fasting and postmethionine tHcy levels both in controls and patients. After 2 months of vitamin supplementation, tHcy (Pre: 17.0 micromol/L [4.0-68]; Post: 7.5 micromol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8 IU/ml [5.1-45.5]; Post: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased, whereas Cy levels showed a small decrease that did not reach statistical significance (Pre: 254 micromol/L [117-466]; Post: 209 micromol/L [168-300]; P=0.3). Patients with the MTHFR 677TT genotype had the major percentage of decrease of tHcy levels with respect to the other genotypes. CONCLUSION: In conclusion, this study demonstrates the presence of elevated Cy plasma levels in renal transplant recipients. Vitamin supplementation reduces tHcy but not Cy levels, and the amount of decrease seems to be influenced by the MTHFR genotype.

5,10-Methylenetetrahydrofolate Reductase (FADH2)↗
PubMed2001

Activation of the immune system and coronary artery disease: the role of anti-endothelial cell antibodies.

On the basis of the role of immuno-mediated inflammation in atherosclerosis we investigated, (1) the prevalence of anti-endothelial cell antibodies (AECA) in ischaemic heart disease (IHD); (2) if beta2-glycoprotein I (beta2-GPI) was the target antigen of AECA; (3) the relationship between AECA, tissue factor (TF) and tissue factor pathway inhibitor (TFPI). In 93 consecutive IHD patients undergoing percutaneous transluminal coronary angioplasty (PTCA) and 105 controls AECA were detected by ELISA on human umbilical vein endothelial cells (HUVEC). AECA positive sera were evaluated for anti-beta2-GPI antibodies by ELISA. TF and TFPI plasma levels were assessed by ELISA. Twelve of 93 (12.9%) IHD patients and only one of 105 controls (0.95%) were AECA positive. The prevalence of AECA was higher in unstable angina (UA) than in effort angina (EA) (P=0.01). Three of 12 AECA positive sera resulted positive for anti-beta2-GPI and showed a marked decrease in EC-binding when tested on HUVEC cultured in serum-free medium. The binding was restored by the addition of beta2-GPI. TF and TFPI levels were similar in AECA positive and AECA negative patients. The rate of angiographically documented clinical recurrences was 66.7% in the AECA positive and 14.8% in the AECA negative group (P=0.0004) with a significant relationship between restenosis and AECA (P<0.0001), unchanged by the inclusion of cardiovascular risk factors in the regression model. Our results suggest a 'role' for AECA in the immune-mediated inflammation in UA beta2-GPI is not the only AECA target antigen. AECA are not responsible for high TF and TFPI levels. The high rate of clinical recurrences after PTCA, confirmed by angiography, in AECA positive patients is in line with such a role and suggests further large-scale 'ad hoc' studies.

Angioplasty, Balloon, Coronary↗
PubMed2001

Lipoprotein (a) and anticardiolipin antibodies are risk factors for clinically relevant restenosis after elective balloon percutaneous transluminal coronary angioplasty.

Recent reports have shown the importance of new risk factors for cardiovascular disease. We investigated the relationship between Lp(a), fibrinolytic parameters and anticardiolipin antibodies (aCL) and the occurrence of clinical recurrence owing to restenosis after elective balloon percutaneous transluminal coronary angioplasty (PTCA) without stenting. In 167 patients, undergoing PTCA, Lp(a) plasma levels, aCL, euglobulin lysis time (ELT), plasminogen activator inhibitor-1 (PAI-1) activity and tissue-type plasminogen activator (t-PA) plasma levels were evaluated before the procedure. During follow-up 29 patients underwent clinical recurrence due to restenosis. Lp(a) levels were significantly higher in patients with restenosis in comparison to those without (P<0.05); an earlier restenosis was observed in patients with Lp(a) values >450 mg/L. Kaplan-Meier survival estimate showed an earlier occurrence of restenosis in patients with base-line Lp(a)>300 mg/l associated with aCL positivity. High Lp(a) plasma levels play a role in the occurrence of clinical recurrence due to restenosis after elective balloon PTCA without stenting; the association with aCL accelerates the development of restenosis.

Adult↗
PubMed2001

S-100 protein and neuron-specific enolase as markers of subclinical cerebral damage after cardiac surgery: preliminary observation of a 6-month follow-up study.

Cerebral damage remains one of the hazards related to cardiac surgery with cardiopulmonary bypass. The use of biochemical markers of cerebral injury may be of practical value. We investigated the plasma release patterns of S-100 protein and neuron-specific enolase (NSE) during the intervention and their relationship with the development of neuropsychological deficits assessed 6 months after the intervention in 16 patients undergoing elective cardiac surgery with cardiopulmonary bypass. Both S-100 and NSE significantly increased peri- and postoperatively. Significant correlations were found between values measured at several time points and impaired performance in a few tests at the 6-month follow-up. A stratification into two age subgroups led to the hypothesis that age might have a confounding or a modifying effect on the association between S-100 and NSE levels, and cognitive impairment.

Aged↗
PubMed2000

Risk factors for cardiovascular disease in renal transplant recipients: new insights.

Long-term survival of renal transplant recipients appears to be influenced by the occurrence of thromboembolic complications and cardiovascular disease. In order to investigate the prevalence of new hemostasis-related risk factors for venous and arterial thrombosis, we investigated 63 renal transplant recipients and 66 age- and sex-matched control subjects. We assayed antiphospholipid antibodies [lupus anticoagulant (LA) and anticardiolipin antibodies (aCL)], lipoprotein (a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), and total homocysteine (tHcy) levels. We found a significantly higher prevalence of positivity for LA (P < 0.001); no difference was detected in the prevalence of aCL between patients and controls. PAI-1 levels were significantly higher in renal transplant recipients than in controls [12.3 IU/ml (2-45.5) vs 7.9 IU/ml (4-18.0); P < 0.0001] with an odd ratio (OR) of 11.8 (4.9-28.5) in univariate analysis and of 5.8 (2.1-15.4) in multivariate analysis. Lp(a) levels were higher in patients then in controls [159 mg/l (1-992) vs 100.5 mg/l (10-412); P < 0.005] with an OR of 5.9 (1.9-18.4) in univariate analysis and of 3.5 (0.9-13.4) in multivariate analysis. Fasting levels of tHcy were significantly higher in renal transplant recipients [7.0 micromol/l (4.0-68) vs 8.1 micromol/l (2.0-24.0); P < 0.00001] with an OR of 40.4 (14.7-111) in univariate analysis and of 33.1 (11.1-115.5) in multivariate analysis. After methionine loading test, we documented levels of tHcy above the 90th percentile of controls in 60/63 patients (95%). Finally, we found a significant correlation between tHcy and PAI-1 plasma levels (r = 0.76; P < 0.000001). Our results show a high prevalence of hemostasis-related risk factors for arterial and venous thrombosis in renal transplant recipients, suggesting the need for the investigation of these patients for the presence of these risk factors in order to improve their long-term survival and to tailor therapy.

Autoantibodies↗
PubMed2000

Videolaparoscopic cholecystectomy induces a hemostasis activation of lower grade than does open surgery.

BACKGROUND: Tissue injury after trauma and surgery may induce alterations in blood coagulation and fibrinolysis, and the hypercoagulable state observed after surgery can be associated with the risk of postoperative thromboembolic complications. Recently, videolaparoscopic (VLPS) cholecystectomy has been introduced, and its advantages over the open procedure seem related to the reduced surgical trauma. The aim of this study was to investigate hemostatic system alterations in patients who undergo open and VLPS cholecystectomy. METHODS: Fibrinogen, prothrombin fragment F1+2, D-dimer, and plasminogen activator inhibitor type-1 (PAI-1) activity was determined in 10 patients who underwent open (group A) and 10 patients who underwent VLPS cholecystectomy (group B), respectively. Blood samples were obtained the day of surgery in the morning (B1), after anesthesia (A1), 1 hour after the start of surgery (S1), then 30 min (E.05) and 24 h (E.24) after the surgery. RESULTS: No significant differences were observed in baseline values between groups A and B for the parameters investigated. At 24 h after surgery, fibrinogen increased significantly (p < 0.05) in group A and also was significantly higher than in group B (p < 0.05). In group A, a marked increase in F1+2 levels (p < 0.01) was observed in all the samples, with the maximum values on the first day after surgery (3.7 nmol/l; 1.2-6.0 nmol/l), whereas in group B, a slight but significant increase in F1+2 levels (2.1 nmol/l; 1.1-3.9 nmol/l; p < 0.01) was observed only 30 min after the end of surgery. In both groups A and B, D-dimer markedly increased after surgery, without statistical significant differences between the two groups at any time. The PAI-1 activity plasma levels remained in the normal range during and after surgery in both groups. CONCLUSIONS: These results indicate that VLPS surgery induces an activation of the clotting system that, although of low degree and short duration, can lead to a transient prothrombotic state.

Adult↗
PubMed2000

Searching for a better assessment of the individual coronary risk profile. The role of angiotensin-converting enzyme, angiotensin II type 1 receptor and angiotensinogen gene polymorphisms.

BACKGROUND: Polymorphisms within renin angiotensin system genes have been investigated as risk factors for coronary artery disease in different populations with contradicting results. The aim of this study was to investigate the genotype distribution and the allele frequencies of ACE, AT1R and AGT gene polymorphisms as coronary artery disease factors and their synergistic effects on coronary risk in an Italian population. METHODS AND RESULTDS: In this study ACE, AT1R and AGT gene polymorphisms were investigated in 205 consecutive coronary artery disease patients and in 209 controls. These polymorphisms were analysed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). The ACE D and AGT 235T allele, but not AT1R C allele, frequency was statistically significant in patients. An association between coronary artery disease and ACE DD, AT1R CC and AGT TT genotype, was found by univariate analysis (OR 2.06 P=0.0007, OR 2.49 P=0.009, OR 1.87 P=0. 019, respectively). At multivariate analysis ACE DD and AT1R CC genotype (OR 1.81 P=0.011, OR 2.61 P=0.011, respectively) remained associated with coronary heart disease. Subjects carrying the ACE DD genotype and AT1R C allele showed a stronger association with myocardial infarction (OR=4.02, P<0.0001). CONCLUSION: Our report indicates the increased risk of coronary artery disease in the presence of ACE DD and AT1R CC genotypes independent of other risk factors, in Italian patients. The present study stresses the relevance of screening for genetic risk factors.

Alleles↗
PubMed2000

High prevalence of mild hyperhomocysteinemia in patients with abdominal aortic aneurysm.

PURPOSE: In vitro studies have recently demonstrated that homocysteine interacts with the aortic wall by inducing both elastolysis and endothelial perturbation. The aim of this study was to evaluate homocysteine plasma levels and their relationships with aortic diameter and endothelial damage in patients with abdominal aortic aneurysm. SUBJECTS AND METHODS: Fifty-eight consecutive male patients (mean age, 69.5 +/- 6.6 years; age range, 49-78 years) who underwent abdominal aortic aneurysm surgery were enrolled in the study. Twenty-two of 58 patients had no clinical or instrumental evidence of atherosclerosis. Sixty control subjects were age matched and sex matched with the patients. In all of the subjects, we evaluated total homocysteine and thrombomodulin plasma levels and the distribution of the C677T methylenetetrahydrofolate reductase gene mutation. RESULTS: Hyperhomocysteinemia was found in 26 (48%) of the 58 patients with abdominal aortic aneurysm, and homocysteine plasma levels were significantly higher in patients than in control subjects (15.7 +/- 6.5 micromol/L vs 9.6 +/- 3.9 micromol/L; P <. 0001). In addition, the subgroup of patients with abdominal aortic aneurysm who did not show evidence of atherosclerosis showed homocysteine plasma levels significantly higher than those in the controls (14.8 +/- 6.1 micromol/L vs 9.6 +/- 3.9 micromol/L; P <. 001). A larger aneurysmal size was detected in hyperhomocysteinemic patients than in those with normal homocysteine plasma levels (5.09 +/- 0.84 cm vs 5.79 +/- 1.5 cm; P <.05). The genotype distribution of the C677T methylenetetrahydrofolate reductase mutation was as follows: TT 21%, TC 55%, and CC 24% in the patients; TT 10%, TC 58%, and CC 32% in the controls. Moreover, in patients a significant correlation (P <.005) between homocysteine plasma level and 677TT methylenetetrahydrofolate reductase genotype was found. Thrombomodulin plasma levels were significantly higher (P <.00005) in patients (median, 30 ng/mL; range, 10-164 ng/mL) than in controls (median, 19 ng/mL; range, 13-44 ng/mL), and thrombomodulin levels were significantly higher (P <.005) in hyperhomocysteinemic patients (median, 39.5 ng/mL; range, 15-164 ng/mL) than in normohomocysteinemic patients (median, 27.5 ng/mL; range, 10-85 ng/mL). In addition, in patients with abdominal aortic aneurysm, a direct significant correlation (P <.005) was found between homocysteine and thrombomodulin. CONCLUSIONS: These data indicate an association between the presence of AAA in patients selected for surgical treatment of AAA and elevated homocysteine plasma levels and suggest that homocysteine may induce endothelial perturbation and stimulation in these patients.

Aged↗
PubMed2000

Angiotensin-converting enzyme DD genotype, angiotensin type 1 receptor CC genotype, and hyperhomocysteinemia increase first-trimester fetal-loss susceptibility.

Complications of pregnancy have been found to be related with thrombophilic polymorphisms that explain about 30% of obstetric complications. We evaluated the angiotensin converting enzyme (ACE) and the angiotensin type 1 receptor (AT1R) gene polymorphisms in the renin-angiotensin system (RAS) as possible risk factors for fetal loss. Fifty-nine women with a history of three or more first-trimester fetal losses and 70 healthy women with a history of normal pregnancies were enrolled in this study. Thrombophilic factors, ACE insertion/deletion (I/D) and AT1R A1166C polymorphisms, prothrombin G20210A and factor V Leiden mutations were analyzed. At univariate and multivariate analysis, a significant association between ACE DD and AT1R CC genotype and fetal loss was observed. The effect of the ACE DD genotype on the risk of fetal loss was higher in AT1R C allele carriers. The prevalence of hyperhomocysteinemia (Hcy) (defined as baseline plasma levels higher than the 95% percentile; cut-off, 10.5 micromol/l per l) was significantly higher in women with fetal loss, and an association between Hcy and fetal loss was detected. All patients showed normal antithrombin, protein C, protein S, and plasminogen activator inhibitor-1 (PAI-1) values. The presence of one risk factor not associated with others was found in 33 out of 59 patients (56%); ACE DD genotype was the most prevalent risk factor. Our results identify new possible predictive markers for fetal loss in RAS polymorphisms and Hcy. Large-scale studies are warranted to attribute clinical relevance to these polymorphisms as risk factors for complicated pregnancies.

Adult↗
PubMed2000

Effect of tourniquet use on activation of coagulation in total knee replacement.

Total knee replacement often is performed with tourniquet application. The advantages of a dry field, including fixation, are well known, but it still is debatable if tourniquet application increases deep vein thrombosis. Measurement of coagulation markers is a well accepted method of studying thrombogenesis activation intraoperatively and postoperatively. Twenty patients undergoing total knee replacement with subarachnoid anesthesia were assigned randomly to two groups: either with tourniquet application (Group I) or without tourniquet application (Group II). There were no differences between patients in the two groups in terms of age, gender, diagnosis (all had osteoarthritis), operative time, and total (intraoperative and postoperative) blood loss. Markers for thrombin generation and fibrinolysis were measured. Blood samples were drawn at four times: baseline before the operation; after bone cuts; after cement fixation (Group II) or 2 minutes after tourniquet deflation (Group I); and 1 hour after surgery. Markers of thrombin generation and fibrinolysis showed a significant increase from baseline in all the patients. In Group II these markers started to increase during surgery, whereas in Group I the increase occurred at the end of the procedure when the tourniquet was deflated. The total amount of thrombin generation was significantly higher in Group II (without tourniquet), whereas fibrinolysis was significantly greater in Group I. Total knee replacement is accompanied by a hypercoagulative state with or without the use of a tourniquet, but it seems to be higher when the tourniquet is not used. In addition, tourniquet application may increase fibrinolysis.

Aged↗
PubMed2000

RAS genes influence exercise-induced left ventricular hypertrophy: an elite athletes study.

PURPOSE: The association of ACE I/D polymorphism with changes in LV mass in response to physical training has been observed, but no association has been found with AT1R A1166C polymorphism. We investigated the ACE I/D, AT1R A1166C, and AT1R CA microsatellite polymorphisms genotype distribution in elite athletes and whether the presence of AT1R C1166 variant, in addition to ACE D allele affects the training-induced LV mass alterations in elite trained athletes. METHODS: The study population comprised 28 healthy players recruited from an Italian elite male soccer team and 155 healthy male subjects. LV mass, LV mass adjusted for body surface area, septal thickness, posterior wall, end-diastolic and end-systolic ventricular dimension, and ejection fraction were determined by echocardiography in pretrained period, at rest and 7 months later during the training. All subjects were genotyped for ACE I/D, AT1R A1166C, and CA microsatellite polymorphisms. RESULTS: Training induced an LV mass increase in all but six athletes. The percentage of athletes in whom an increase of LV mass was found after training was statistically different in relation to the ACE D allele: no increase was observed in three of 24 D allele carriers and in three of four II genotype players (Fisher's exact test, P = 0.02). As AT1R is concerned, no increase was observed in 4 of 15 C allele carriers and in 2 of 13 AA genotype athletes (Fisher's exact test, P > 0.05). The contemporary presence of ACE D and AT1R C allele did not affect the changes after training. No difference has been observed in the CA microsatellite marker allele frequencies between athletes and controls (P = 0.46). CONCLUSION: In this study, we provide the evidence that soccer play does not select athletes on genotype basis. Training-induced LV mass changes in male elite athletes are significantly associated with the presence of ACE D allele, but not of AT1R C allele.

Adult↗
PubMed2000

Tissue factor and homocysteine levels in ischemic heart disease are associated with angiographically documented clinical recurrences after coronary angioplasty.

BACKGROUND: In ischemic heart disease (IHD) patients high plasma levels of Tissue Factor (TF), the trigger of coagulation cascade, are present. Homocysteine (Hcy) is a risk factor for coronary artery disease, and several different pathophysiological mechanisms by which Hcy may play a role in thrombus formation have been postulated in "in vitro" studies. We investigated the "in vivo" role of Hcy in affecting plasma levels of TF, its inhibitor Tissue Factor Pathway Inhibitor (TFPI) and hypercoagulability. METHODS AND RESULTS: We investigated 119 IHD patients who underwent PTCA and compared them with 103 healthy subjects. TF, TFPI, Thrombin-Antithrombin complexes (TAT) and Hcy levels were significantly higher in the patients than in the controls. A positive correlation was found between Hcy and TF (r = 0.54; p < 0.0001), Hcy and TFPI (r = 0.26; p <0.05) as well as Hcy and TAT (r = 0.33; p <0.0001) levels. An inverse correlation existed between folate intake and Hcy levels (r = -0.28; p = 0.001). Hcy levels within the first quartile and in the highest quartile were associated with a lower (p < 0.001) and higher (p <0.0001) rate of clinical recurrences, respectively. Patients with TF values in the first quartile had a lower rate of angiographically documented clinical recurrences as compared to those in the fourth quartile (p <0.01); those in the highest quartile of TF showed a higher rate of recurrences (p = 0.001). Multivariate analysis confirmed these results (first quartile of Hcy: OR 0.02, C1 0.002-0.27; fourth quartile of Hcy: OR 36.5, C1 3.6-365/first quartile of TF: OR 0.006, C1 0.001-0.44; fourth quartile of TF: OR 16.4, C1 3.0 - 90.0), also after adjustment for risk factors and Hcy and TF respectively. CONCLUSIONS: In this study we show that TF, TFPI and TAT levels are correlated with Hcy plasma levels in IHD patients, providing evidence of an "in vivo" pathophysiological mechanism of hyperhomocysteinemia. The observed association between angiographically documented clinical recurrences and TF and Hcy values awaits confirmation in studies designated to evaluate this issue on a larger number of patients.

Adult↗
PubMed1999

Multiple primary tumors of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?

Head-and-neck cancer (HNC) patients have a high risk of developing second primary tumors of the upper aerodigestive tract, the main cause of death. Although the roles of tobacco and diet in multiple head-and-neck carcinogenesis have been thoroughly investigated, little is known about individual genetic susceptibility factors involved in this process. Genomic instability, reflecting the propensity and the susceptibility of the genome to acquire multiple alterations, could be considered a driving force behind multiple carcinogenesis. Mutation of the p53 tumor-suppressor gene has been proposed to play an important role in this process. Therefore, we evaluated the incidence of inherited p53 germ-line alteration(s) in a population of 24 consecutive HNC patients and their first-degree relatives affected by multiple malignancies as well as the occurrence of p53 somatic acquired mutation(s) in 16 cancers, including first and second primaries from 5 HNCs of the same group. Mutations in exons 4-11 of the p53 gene were investigated using SSCP-PCR analysis and DNA sequencing. Analysis was extended to the peripheral blood and cancer biopsies available from first-degree relatives of cancer-prone families with p53 germ-line mutations. p53 germ-line mutations were identified in the peripheral blood and corresponding cancers of 3 HNC patients who had multiple malignancies. The only missense mutation detected was mapped in exon 6; it is a GTG to GAG substitution with an amino acid change from Val to Glu at codon 197. The remaining 2 p53 germ-line mutations were single-nucleotide substitutions without amino acid change in exon 6 (codon 213, CGA to CGG) and in exon 8 (codon 295, CCT to CCC), respectively. These mutations were found in HNC patients with a family history of cancer. Abnormal expression of wild-type p53 protein in normal and pathological tissues from patients with the same sense single-nucleotide substitutions was detected by immuno-histochemistry.

Adult↗
PubMed1999

A heterozygous splice site mutation in COL6A1 leading to an in-frame deletion of the alpha1(VI) collagen chain in an italian family affected by bethlem myopathy.

Bethlem myopathy is a mild neuromuscular disorder with proximal muscular weakness and early flexion contractures. It is an autosomal dominant disease due to mutations in type VI collagen genes. We found a T-->C substitution at the +2 position of COL6A1 intron 14 in a family, leading to skipping of exon 14 and an in-frame deletion of 18 amino acids in the triple-helical domain of the alpha1(VI) collagen chain. The deletion included a cysteine residue believed to be involved in the assembly of type VI collagen dimers intracellularly, prior to the protein secretion. Analysis of the affected fibroblasts showed that the shortened alpha1(VI) collagen chains were synthesized but not secreted by the cells and that the amount of type VI collagen microfibrils deposited by the cells was reduced. The results suggest that the clinical phenotype is due to a reduction in the level of type VI collagen in the extracellular matrix.

Adult↗
PubMed1999

Microheterogeneity in the distribution of the 844ins68 in the cystathionine beta-synthase gene in Italy.

Cystathionine beta-synthase (CBS) is an important enzyme for methionine metabolism. A common 844ins68 insertion variant in the CBS gene has been described. This 68-bp duplication of the intron 7-exon 8 boundary within the CBS gene already has been reported to be associated in cis with the T833C mutation. Heterozygosity for CBS deficiency is considered an important cause of hyperhomocysteinemia that strongly relates to cardiovascular disease, as well as homozygosity for another common variant, the C677T mutation of 5,10-methylene tetrahydrofolate reductase. We analysed the prevalence of the 844ins68 variant in the CBS gene in 595 unrelated apparently healthy individuals from nine Italian regions and in 133 patients with coronary artery disease. Our data confirm that the T833C mutation cosegregates in cis with the 844ins68 in all carriers of the insertion. Furthermore, no statistical difference was found in the insertion variant allele frequency between controls and coronary artery disease patients. Our study indicates a microheterogeneity in the distribution of the 844ins68 in the Italian population.

Cystathionine beta-Synthase↗
PubMed1999

World distribution of the T833C/844INS68 CBS in cis double mutation: a reliable anthropological marker.

Mild hyperhomocysteinemia is associated to mutations either in cystathionine beta-synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In 1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common CBS mutation (T833C) detected in homocystinuric patients. Recently, this double mutation has been detected in Italian and North-American controls. Compared to a group of patients affected by coronary artery disease, North-American controls showed not statistically significant difference. Moreover, Italian controls displayed a microheterogeneity in the mutant allele frequency distribution depending on their geographical origin (North or South of Italy). Aim of our study was to evaluate the prevalence of the double in cis mutation in different populations. We studied 377 healthy subjects belonging to various human groups. Genomic DNA, extracted from peripheral blood samples, was amplified using specific primers; PCR fragments were digested with Bsr I restriction enzyme to detect the double mutation. Our data show a significant heterogeneity among the populations studied, therefore this mutation turned out to be a reliable anthropogenetic marker. The distribution of the double mutation will contribute, with other DNA polymorphisms, to evaluate the genetic admixture of mixed populations such as Afro-Americans.

Alleles↗