Publications (23)90.99 Total impact
-
Article: Fluoropyrimidine toxicity in patients with dihydropyrimidine dehydrogenase splice site variant: the need for further revision of dose and schedule.
[show abstract] [hide abstract]
ABSTRACT: Dihydropyrimidine dehydrogenase (DPD) is a key enzyme in the metabolic catabolism of 5-fluorouracil (5-FU) and its derivatives (capecitabine and tegafur). Complete or partial deficiency of DPD activity has been demonstrated to induce severe toxicities in cancer patients treated with fluoropyrimidine therapy. We analyzed 180 individuals that were candidates for a treatment with 5-FU class drugs for the most common DPD mutation, IVS14+1G>A, and detected four heterozygous patients. We recorded the toxicities for all 180 individuals after the first two chemotherapy cycles and found that three of the four patients, although they were treated with a dose reduction in 50 % on the basis of the genetic analysis, all showed severe toxicities that resulted in hospitalization of patient and premature discontinuation of treatment. One patient with mutated DPD was not treated with chemotherapy upon the clinician's decision because of his DPD mutated genotype and the presence of microsatellite instability. Our data suggest that greater dose reductions or alternative therapies are needed for patients with DPD IVS14+1G>A mutations.Internal and Emergency Medicine 04/2013; · 2.06 Impact Factor -
Article: Elevation of Angiotensin-II Type-1-Receptor Autoantibodies Titer in Primary Aldosteronism as a Result of Aldosterone-Producing Adenoma.
[show abstract] [hide abstract]
ABSTRACT: The mechanisms of excess aldosterone secretion in primary aldosteronism (PA) remain poorly understood, although a role for circulating factors has been hypothesized for decades. Agonistic autoantibodies against type-1 angiotensin-II receptor (AT1AA) are detectable in malignant hypertension and preeclampsia and might play a role in PA. Moreover, if they were elevated in aldosterone-producing adenoma (APA) and not in idiopathic hyperaldosteronism (IHA), they might be useful for discriminating between these conditions. To test these hypotheses, we measured the titer of AT1AA in serum of 46 patients with PA (26 with APA, 20 with IHA), 62 with primary hypertension (PH), 13 preeclamptic women, and 45 healthy normotensive blood donors. We found that the AT1AA titer was higher (P<0.05) in both PA and PH patients (2.65±1.55 and 1.86±0.63, respectively) than in normotensive subjects (1.00±0.20). In APA, it was 2-fold higher than in IHA patients (3.43±1.20 versus 1.64±1.39, respectively, P<0.001), despite similar blood pressure values. Of note, it allowed effective discrimination of APA from either PH or IHA, as shown by Receiver Operator Characteristics curve analysis. Moreover, after captopril challenge, plasma aldosterone concentration fell more in AT1AA-positive than in AT1AA-negative PA patients (-32.4% [21.1-42.9] versus 0.0% [0.0-22.6], P=0.015), suggesting an agonistic role for these autoantibodies. Thus, a higher serum AT1AA titer in patients with APA than in IHA and PH patients can be useful in differentiating APA patients from either PH or IHA, and thus in selecting PA patients to be submitted to adrenal vein sampling.Hypertension 12/2012; · 6.21 Impact Factor -
Article: Haptoglobin phenotype and epithelial ovarian cancer.
[show abstract] [hide abstract]
ABSTRACT: Haptoglobin (H) is a glycoprotein that regulates the immune response. Serum haptoglobin levels are significantly higher in patients with advanced epithelial ovarian cancer (EOC) with poor survival. Different isoforms of haptoglobin have been found in the serum of patients with EOC. We studied the genetic susceptibility and outcome of patients with EOC correlated to H phenotypes. Analyses of the H phenotypes were performed on sera from patients stored at -70°C. A modified method based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of sera was used, followed by western blotting. Seventy-nine consecutive patients with EOC and 63 healthy women were enrolled. Their mean (±S.D.) age was 58.9±12.46 years. Overall survival was 66 months (95% confidence interval=37.7-94.2). Similar distribution of haptoglobin phenotypes was observed in EOC and in healthy women. No significant correlation was found between haptoglobin phenotype, overall survival and time-to-progression. Fewer G3 tumors were found in patients with H2-2 compared with those with H1-2 (84.2% and 90.6%, respectively, p<0.04). No significant correlation was found between H phenotype and tumor markers or number of relapses. Although ours is a preliminary study based on a small population with scant significant findings, we hypothesize that patients with EOC with haptoglobin 2-2, might have a better prognosis because they present fewer G3 tumors and they may present a stronger immune response than patients with 1-1 and 1-2 phenotypes. Larger studies should be performed to assess the predictive value of haptoglobin phenotype in patients with EOC.Anticancer research 10/2012; 32(10):4353-8. · 1.73 Impact Factor -
Article: CC chemokine receptor 5 polymorphism in Italian patients with Behcet's disease.
[show abstract] [hide abstract]
ABSTRACT: Objective. To evaluate the potential role of CC chemokine receptor 5 (CCR5)Δ32 polymorphism in the susceptibility to and clinical expression of Behçet's disease (BD) in a cohort of Italian patients.Methods. One hundred and ninety-six consecutive Italian patients satisfying the ISG criteria for BD were followed up for 8 years, and 180 healthy age- and sex-matched blood donors were molecularly genotyped for the CCR5Δ32 polymorphism. A standard microlymphocytotoxicity technique was used to serotype HLA-B51. The patients were subgrouped on the basis of the presence or absence of clinical manifestations.Results. The distribution of the CCR5Δ32 genotype differed between BD patients and controls (P = 0.02). The CCR5Δ32 allele was more common in BD patients than in controls [P = 0.02, odds ratio (OR) 2.28 (95% CI 1.1, 4.8)]. Carriers of the CCR5Δ32 allele (Δ32/Δ32 + CCR5/Δ32) were significantly more common in BD patients than in controls [P = 0.02, OR 2.37 (95% CI 1.1, 5.1)]. Population-attributable risk was 7.1%. In categorizing patients according to gender, the association between CCR5Δ32 polymorphism and BD was similar in females and males (ORs 2.76 and 2.0, respectively). No significant differences were found when the frequencies of clinical manifestations were compared between CC5RΔ32 allele carriers and non-carriers.Conclusion. CCR5Δ32 polymorphism is associated with an increased susceptibility to develop BD. Chemokines may have a role in the pathophysiology of BD.Rheumatology (Oxford, England) 09/2012; · 4.24 Impact Factor -
Article: IL-23A, IL-23R, IL-17A and IL-17R polymorphisms in different psoriatic arthritis clinical manifestations in the northern Italian population.
[show abstract] [hide abstract]
ABSTRACT: To investigate the genetic variability of IL-17A, IL17-RA, IL-23A and IL-23R genes on an in-depth phenotypically characterized northern Italian Psoriatic arthritis (PsA) case-control cohort, in search for associations specific to different PsA clinical sub-phenotypes. We examined 118 patients with PsA according to CASPAR criteria (mean age 57 ± 13, female 38.4 %, mean disease duration 13.9 ± 8.6 years, peripheral disease 83.8 %, axial manifestations 34.5 %, radiological erosive disease 49 %) compared with 248 controls of the same ethnic origin matched for age and sex. The presence of axial disease was defined by the clinical axial involvement and/or the presence of radiological alteration consistent with spondyloarthropathy according to New York criteria. The presence of peripheral disease (arthritis and/or enthesitis) was defined only on clinical basis. A total of 40 SNPs, mapping within the genes mentioned above, were genotyped in both groups and used to perform association analyses by subdividing the PsA sample into subgroups according to different clinical manifestations on the basis of axial and peripheral involvements. No differences between patients and controls were found in the distribution of the IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants. Comparing patients with axial disease versus those without, we found that axial manifestations were significantly associated with the presence of IL-23R rs12401432 GG homozygosity (26.8 % vs. 5.3 %, p (corr) = 0.019, OR 2.63 [95 % CI 1.13-6.16]). No differences in distribution of the allelic variants were found comparing patients with versus those without peripheral disease or patients with versus without radiological peripheral erosions. In PA patients of northern Italian origin, IL-17A, IL17-RA, IL-23A and IL-23R genes allelic variants are not associated with disease susceptibility. However, a strong association with the IL-23RA rs12401432 GG genotype is associated with axial involvement of the disease.Rheumatology International 09/2012; · 1.88 Impact Factor -
Article: Very Early Onset and Severe Complicated Phenotype Caused by a New Spastic Paraplegia 3A Gene Mutation.
[show abstract] [hide abstract]
ABSTRACT: Spastic paraplegia 3A is the second most common form of hereditary autosomal dominant spastic paraplegia. This form is mainly associated with an early age of onset and pure phenotype, although recently complicated forms were reported. We describe a patient carrying a new C>T P344S>CT mutation in exon 10 of the spastic paraplegia 3A gene with unusual, complicated, and extremely severe phenotype. At the last neurologic examination performed at 17 years of life, the patient disclosed spastic tetraparesis, sensorimotor axonal neuropathy, cognitive and cranial nerve impairment, mild pes cavus, and distal amyotrophy.Journal of child neurology 02/2012; 27(10):1348-50. · 1.59 Impact Factor -
Article: PLA1/A2 polymorphism of the platelet glycoprotein receptors IIIA in Behçet's disease.
[show abstract] [hide abstract]
ABSTRACT: To investigate potential associations between the PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA (GpIIIa) gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD). Two hundred consecutive Italian patients satisfying the International Study Group criteria for BD who were followed up for seven years and 241 healthy Italian age- and gender-matched blood donors were molecularly genotyped for the PlA1/A2 polymorphism of the platelet GpIIIa gene; 118 and 117 of the 200 BD patients were also respectively genotyped for factor V Leiden and prothrombin gene G20210A polymorphisms. A standard microlymphocytotoxicity technique was used to type serological HLA class B51. The patients were grouped on the basis of the presence or absence of clinical manifestations. The diagnoses of deep vein thrombosis (DVT) and superficial thrombophlebitis were initially made clinically, and then confirmed by means of ultrasonography or contrast venography. The distribution of the PlA1/A2 genotype was investigated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. The allele and genotype frequency of the PlA1/A2 polymorphism were not significantly different in the BD patients and controls, but the PlA2 allele was significantly more frequent in the BD patients with DVT than the controls (p=0.023; Pcorr=0.046; OR 2.0, 95% CI 1.1-3.7). There were no associations between thrombotic events and the PlA1/A2 polymorphism in the BD patients carrying factor V Leiden or prothrombin gene G20210A mutations. The PlA2 allele was significantly less frequent in the BD patients with genital genital ulcers than in those without (26.9% vs. 43.2%; p=0.022; P corr 0.044; OR 0.48, CI 0.27-0.88). The PlA1/A2 polymorphism of the GpIIIa gene was associated with DVT in our Italian BD patients, but does not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations. There was a negative association between the A2 allele and genital ulcers.Clinical and experimental rheumatology 07/2011; 29(4 Suppl 67):S38-43. · 2.15 Impact Factor -
Article: A clinical phenotype mimicking essential hypertension in a newly discovered family with Liddle's syndrome.
[show abstract] [hide abstract]
ABSTRACT: Liddle's syndrome (LS) is a monogenic form of hypertension simulating a mineralocorticoid excess, and is currently suspected in young hypokalemic hypertensives. The aims of the study were: (i) to evaluate the clinical phenotype of LS in a newly identified Italian family of Sicilian origin carrying a gain-of-function mutation of the β subunit of the epithelial sodium channel (ENaC) (P617L) previously reported by our group in an apparently unrelated Sicilian patient presenting the typical phenotype of LS including hypokalemia; (ii) to determine whether an unknown biological relationship exists between the newly identified family and the family of the proband previously reported. Genetic analysis was performed in the present family, in the individual in which the βP617L mutation was first observed, and in his relatives. βP617L mutation was identified in the proband and in three maternal relatives. None of them showed hypokalemia. Mild to severe early onset hypertension and left ventricular hypertrophy were present in all of them. Analysis of mitochondrial DNA (mtDNA) and Y chromosome profiles in the present family and in the proband's family previously reported showed the absence of a relationship between them. The availability of only one carrier of the mutation in one of the two families meant that a genetic analysis able to assess a founder effect was not feasible. LS should be considered in all cases of early onset hypertension, independently of the plasma potassium concentration. The incidence of LS may be greater than is currently thought, because hypokalemia is not invariably present.American Journal of Hypertension 04/2011; 24(8):930-5. · 3.18 Impact Factor -
Article: Increase in clusterin forms part of the stress response in Hodgkin's lymphoma.
[show abstract] [hide abstract]
ABSTRACT: Clusterin (also called APOJ, SGP-2, XIP8) has thus far been only partially characterized in lymphomas contrary to other types of cancer. Its expression has been reported only for anaplastic large cell lymphomas and, more recently, in mycosis fungoides. Here, we demonstrate an up-regulation of intracellular clusterin in Hodgkin's lymphoma (HL)-derived cell lines L-428, KM-H2 and L-540, caused by different stimuli such as IFN-γ, doxorubicin and X-rays. These stimuli are relevant for the pathophysiology and therapy of HL and represent a first step in the characterisation of this glycoprotein known to have a role in drug chemoresistance. p53 up-regulation accompanies increases in clusterin levels accordingly with the onset of apoptosis. We also show that the cells secrete more clusterin after treatment with doxorubicin, which is consistent with the observed intracellular increase. These observations suggested that the levels of circulating clusterin should also be measured in the peripheral blood from HL patients both at the time of diagnosis and after two cycles of chemotherapy. In a preliminary study on patient sera we observed that an increase in clusterin is correlated with positron emission tomography (PET) positivity after two cycles of chemotherapy.International Journal of Oncology 03/2011; 38(3):677-84. · 2.40 Impact Factor -
Article: CC chemokine receptor 5 polymorphism in chronic periaortitis.
[show abstract] [hide abstract]
ABSTRACT: Chronic periaortitis (CP) is a rare disease characterized by a fibro-inflammatory tissue surrounding the abdominal aorta, and includes non-aneurysmal [idiopathic retroperitoneal fibrosis (IRF)] and aneurysmal forms [inflammatory abdominal aortic aneurysm (IAAA)]. We investigated whether CC chemokine receptor 5 (CCR5)Δ32 polymorphism confers susceptibility to CP. One hundred CP patients and 180 healthy controls were genotyped for CCR5Δ32 polymorphism by molecular methods. The patients were subgrouped according to the type of CP (IRF or IAAA) and the presence of established atherosclerotic disease (ischaemic heart disease, cerebrovascular disease and peripheral arterial disease). The distribution of the CCR5Δ32 genotype differed between CP patients and controls (P = 0.01). The CCR5Δ32 allele was more frequent in CP patients than in controls [P = 0.02, odds ratio (OR) 2.8 (95% CI 1.2, 6.4)]. The distribution of the CCR5Δ32 genotype did not differ significantly between IRF patients and controls, whereas the CCR5Δ32 allele was more frequent in IAAA patients than in controls [P = 0.0001, OR 10.0 (95% CI 3.7, 27.3)]. Furthermore, the CCR5Δ32 allele occurred more frequently in IAAA than in IRF patients [P = 0.001, OR 6.4 (95% CI 2.1, 19.1)]. The CCR5Δ32 allele frequency was higher in IAAA patients without established atherosclerotic disease compared with controls [66.7 vs 5.6%, P = 0.00001, OR 34.0 (95% CI 7.4, 156.3)], but not in IAAA patients with atherosclerotic disease and IRF patients with or without atherosclerotic disease. The CCR5Δ32 polymorphism might be associated with an increased risk of developing the aneurysmal form of CP, IAAA, particularly in patients without established atherosclerotic disease. Chemokines may have a role in the pathophysiology of CP.Rheumatology (Oxford, England) 01/2011; 50(6):1025-32. · 4.24 Impact Factor -
Article: G/R 241 polymorphism of intercellular adhesion molecule 1 (ICAM-1) is associated with Fuchs uveitis.
[show abstract] [hide abstract]
ABSTRACT: To investigate potential associations of the ICAM-1 gene polymorphisms and Fuchs uveitis in a cohort of Italian patients. Seventy-one consecutive Italian patients affected by Fuchs uveitis were observed at the Ocular Immunology Unit, Arcispedale S. Maria Nuova (Reggio Emilia, Italy) from 2002 to 2008. Two hundred twenty-six healthy Italian blood donors from the same geographic area were selected as the control group. All Fuchs uveitis patients and control subjects were genotyped by polymerase chain reaction (PCR) and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4). The frequency of the ICAM-1 G/R 241 polymorphism was significantly higher in Fuchs uveitis than in the control subjects (16.9% vs. 5.8%; P=0.006, Pcorr=0.012; odds ratio, 3.3; 95% confidence interval, 1.4-7.7). No significant association between clinical features and ICAM-1 polymorphisms was found. This study demonstrates for the first time that the ICAM-1 G/R 241 polymorphism may represent a candidate gene for Fuchs uveitis susceptibility.Investigative ophthalmology & visual science 05/2010; 51(9):4447-50. · 3.43 Impact Factor -
Article: Hereditary spastic paraplegia and axonal motor neuropathy caused by a novel SPG3A de novo mutation.
[show abstract] [hide abstract]
ABSTRACT: Mutations in the SPG3A gene (atlastin protein) cause approximately 10% of autosomal-dominant hereditary spastic paraplegia. Most patients with an SPG3A mutation present with a pure phenotype and early-onset disease, although complicated forms with peripheral neuropathy are also reported. We report a new heterozygous S398F mutation in exon 12 of the SPG3A gene causing a very early-onset spastic paraplegia in association with motor axonal neuropathy in a 4-year-old girl resembling diplegic cerebral palsy.Brain & development 10/2009; 32(7):592-4. · 1.74 Impact Factor -
Article: Liddle's syndrome caused by a novel missense mutation (P617L) of the epithelial sodium channel beta subunit.
[show abstract] [hide abstract]
ABSTRACT: The aim of the study was to search for mutations of SCNN1B and SCNN1G in an Italian family with apparently dominant autosomal transmission of a clinical phenotype consistent with Liddle's syndrome. Genetic analysis was performed in the proband, his relatives, and 100 control subjects. To determine the functional role of the mutation identified in the proband, we expressed the mutant or wild-type epithelial sodium channel in Xenopus laevis oocytes. A novel point mutation, causing an expected substitution of a leucine residue for the second proline residue of the conserved PY motif (PPP x Y) of the beta subunit was identified in the proband. The functional expression of the mutant epithelial sodium channel in X. laevis oocytes showed a three-fold increase in the amiloride-sensitive current as compared with that of the wild-type channel. This newly identified mutation adds to other missense mutations of the PY motif of the beta subunit of the epithelial sodium channel, thus confirming its crucial role in the regulation of the epithelial sodium channel. To our knowledge, this is the first report of Liddle's syndrome in the Italian population, confirmed by genetic and functional analysis, with the identification of a gain-of-function mutation not previously reported.Journal of Hypertension 06/2008; 26(5):921-7. · 4.02 Impact Factor -
Article: PlA1/A2 polymorphism of the platelet glycoprotein receptor IIIA and risk of cranial ischemic complications in giant cell arteritis.
[show abstract] [hide abstract]
ABSTRACT: To investigate potential associations of the PlA1/A2 polymorphism of the platelet glycoprotein IIIa (GPIIIa) gene with susceptibility to, and clinical expression of, giant cell arteritis (GCA). One hundred forty patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 241 population-based healthy controls from the same geographic area were genotyped for the PlA1/A2 polymorphism of the platelet GPIIIa gene by molecular methods. The patients were divided into subgroups according to the presence or absence of polymyalgia rheumatica and cranial ischemic complications. The distribution of the PlA1/A2 genotype was investigated, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. The distribution of the PlA1/A2 genotype differed significantly between GCA patients with and those without visual loss caused by anterior ischemic optic neuritis (P = 0.016, corrected P [P(corr)] = 0.048). The PlA2 allele was found significantly more frequently in GCA patients with anterior ischemic optic neuritis than in those without anterior ischemic optic neuritis (P = 0.023, P(corr) = 0.046, OR 2.4 [95% CI 1.2-4.8]). Homozygosity for the PlA2 allele was significantly more frequent among GCA patients with anterior ischemic optic neuritis than among those without (P = 0.019, P(corr) = 0.038, OR 7.1 [95% CI 1.64-30.6]). Cranial ischemic complications occurred in 8 of 19 patients (42.1%) receiving antiplatelet therapy, compared with 22 of 118 patients (18.6%) not receiving such therapy (P = 0.03, OR 3.2 [95% CI 1.1-8.8]). Our findings show that A2/A2 homozygosity is associated with an increased risk of visual loss due to anterior ischemic optic neuritis in GCA patients. Antiplatelet therapy, however, was not effective in reducing the risk of ischemic events in this population of GCA patients.Arthritis & Rheumatism 11/2007; 56(10):3502-8. · 7.87 Impact Factor -
Article: Interleukin-10 promoter polymorphisms in giant cell arteritis.
[show abstract] [hide abstract]
ABSTRACT: To investigate potential associations between interleukin-10 (IL-10) promoter polymorphisms and susceptibility to, and clinical features of, giant cell arteritis (GCA). A total of 140 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 200 population-based controls from the same geographic area were genotyped for promoter polymorphisms of the IL-10 gene, by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica (PMR) and ischemic complications (any or all of the following: vision loss, jaw claudication, cerebrovascular accidents, or aortic arch syndrome). The distribution of the C/A 592 genotype differed significantly between the GCA patients and the controls (P(corr) = 0.003). Carriers of the A592 allele (A/A or C/A) were significantly more frequent among the GCA patients than among the controls (P(corr) = 0.004, odds ratio [OR] 2.0 [95% confidence interval (95% CI) 1.3-3.1]). Homozygosity for the A592 allele was significantly more frequent among the GCA patients than among the controls (P(corr) = 0.002, OR 3.4 [95% CI 1.6-7.2]). The distribution of the A/G 1082 genotype was similar in GCA patients and controls. In the haplotype analysis, the frequency of the ATA haplotype was significantly higher in GCA patients than in the controls (P = 0.0001), whereas the frequencies of the ACC and GTA haplotypes were significantly lower (P = 0.0001 for both comparisons). No significant associations were found for comparisons of GCA patients with and those without PMR or GCA patients with and those without ischemic complications. Our findings show that the -592 C/A promoter polymorphism of the IL-10 gene is associated with susceptibility to GCA.Arthritis & Rheumatism 01/2007; 54(12):4011-7. · 7.87 Impact Factor -
Article: Relationship between interleukin 6 promoter polymorphism at position -174, IL-6 serum levels, and the risk of relapse/recurrence in polymyalgia rheumatica.
[show abstract] [hide abstract]
ABSTRACT: To assess the role of -174 G/C promoter polymorphism of interleukin 6 (IL-6) in the susceptibility to polymyalgia rheumatica (PMR). We also investigated whether this polymorphism modulates the circulating level of IL-6 and the risk of relapse/recurrence in a series of patients with PMR followed up prospectively. A prospective study of 112 consecutive, untreated patients with isolated PMR (i.e., without evidence of giant cell arteritis) who were followed up for at least 24 months. This cohort represented all patients diagnosed over a 5-year period in one Italian rheumatological secondary referral center. Patients were monitored for clinical signs/symptoms and acute-phase reactants. All PMR patients and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. IL-6 serum levels were measured in 67 PMR patients and 43 population-based controls. The distribution of the G/C 174 genotype was similar in PMR patients and controls. No significant associations with IL-6 promoter polymorphism at position -174 were found when PMR patients with and without relapse/recurrence were compared. Controls homozygous for the C allele had higher serum IL-6 levels than the carriers of the G allele (4.5 +/- 3.7 pg/ml vs 1.8 +/- 2.1 pg/ml, p = 0.01). Patients homozygous for the allele C had significantly higher values of IL-6 during followup than patients carrying GC or GG genotypes. CC homozygosity was significantly more frequent in patients with persistently elevated levels of IL-6 than in those without. The presence of persistently elevated IL-6 levels, but not the CC genotype, was associated with an increased frequency of relapse/recurrence. Our findings show that the 174 G/C promoter IL-6 polymorphism is not implicated in susceptibility to PMR. However, CC genotype characterized PMR patients with persistently elevated levels of IL-6 who are at higher risk of developing relapse/recurrence. A genetically modulated pattern of IL-6 production could affect the longterm outcome of patients with PMR.The Journal of Rheumatology 05/2006; 33(4):703-8. · 3.69 Impact Factor -
Article: High risk of cutaneous melanoma amongst carriers of the intercellular adhesion molecule-1 R241 allele.
[show abstract] [hide abstract]
ABSTRACT: We examined the relation between cutaneous melanoma risk and the intercellular adhesion molecule-1 (ICAM-1) gene single nucleotide polymorphisms G241R and K469E, as well as the circulating soluble form of ICAM-1 determined in plasma, in the population of Modena Province, northern Italy. Individuals carrying at least one R241 allele, versus those carrying the wild-type GG genotype, had a relative risk of melanoma of 4.3 (P = 0.022), whereas the K469E polymorphism was unrelated to disease risk. Soluble ICAM-1 levels above 10 ng/ml directly and strongly correlated with melanoma risk. In this population, individuals carrying the R241 allele of the ICAM-1 gene appeared to show an enhanced susceptibility to cutaneous melanoma, possibly because of increased ICAM-1 expression.Melanoma Research 03/2006; 16(1):93-6. · 2.19 Impact Factor -
Article: Interleukin-6 promoter polymorphism at position -174 in giant cell arteritis.
[show abstract] [hide abstract]
ABSTRACT: To investigate potential associations between the -174 G/C interleukin-6 (IL-6) promoter polymorphism and susceptibility to and clinical features of giant cell arteritis (GCA), particularly in patients with or without polymyalgia rheumatica (PMR) and with or without ischemic complications. One hundred and twenty-six patients with biopsy-proven GCA who were residents in Reggio Emilia, Italy, and 112 population-based controls from the same geographic area were genotyped for IL-6 polymorphism at position -174 by molecular methods. Patients were divided in subgroups according to presence or absence of PMR and ischemic complications (visual loss, jaw claudication, cerebrovascular accidents, aortic arch syndrome). Distribution of the G/C 174 genotype was similar in patients with GCA and controls. No significant associations with the IL-6 promoter polymorphism at position -174 were found when GCA patients with or without PMR or with or without ischemic complications were compared. Further, IL-6 genotypes did not significantly affect levels of C-reactive protein or other inflammatory markers at diagnosis. Our findings show that the 174 G/C promoter IL-6 polymorphism does not seem to be implicated in susceptibility to and clinical expression of GCA.The Journal of Rheumatology 12/2005; 32(11):2173-7. · 3.69 Impact Factor -
Article: Vascular endothelial growth factor gene polymorphisms in Behçet's disease.
[show abstract] [hide abstract]
ABSTRACT: To evaluate potential associations of vascular endothelial growth factor (VEGF) gene polymorphisms with Behçet's disease (BD) and disease expression. Case patients were 122 consecutive Italian patients with BD followed at the Rheumatology, Ophthalmology, and Neurology Units in Bologna, Ferrara, Milano, Palermo, Potenza, Prato, Reggio Emilia, and Trento over a 3-year period (1997-99) and who satisfied the International Study Group criteria for BD. Also selected as a control group were 200 healthy age and sex matched blood donors. All patients with BD and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for +936 C/T (rs3025039) and -634 C/G (rs2010963) mutations and for an 18 base pair (bp) insertion/deletion (I/D) polymorphism at -2549 of the the VEGF promoter region. In vitro release of VEGF by peripheral blood mononuclear cells (PBMC) was investigated by ELISA in healthy controls homozygous for the polymorphisms studied. The carriage rates of the alleles I and -634C were significantly more frequent in patients with BD than in healthy controls [p corr = 0.036, OR 1.8 (95% CI 1.1-2.9) and p corr = 0.05, OR 1.8 (95% CI 1.1-3.0), respectively]. While the distribution of allele +936T was similar in patients with BD and healthy controls, its frequency was significantly higher in BD patients with posterior uveitis/retinal vasculitis than in those without (p = 0.022, OR 2.4, 95% CI 1.1-5.0). Lipopolysaccharide-stimulated VEGF production from PBMC of healthy subjects was higher in II homozygous than in DD homozygous. Our data indicate that carriers of -634C and I alleles are associated with susceptibility to developing BD.The Journal of Rheumatology 10/2004; 31(9):1785-9. · 3.69 Impact Factor -
Article: Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritis.
[show abstract] [hide abstract]
ABSTRACT: To examine potential associations of the Glu/Asp(298) polymorphism in exon 7 and the 4a/b polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) gene with susceptibility to and clinical expression of giant cell arteritis (GCA), particularly in patients with versus those without ischemic complications. Ninety-one consecutive patients with biopsy-proven GCA, who were residents of Reggio Emilia, Italy, and 133 population-based controls from the same geographic area were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for eNOS polymorphisms in exon 7 and intron 4. The patients were separated into 2 subgroups according to the presence or absence of ischemic complications (visual loss and/or jaw claudication and/or aortic arch syndrome). The distribution of the Glu/Asp(298) genotype differed significantly between GCA patients and controls (corrected P [P(corr)] = 0.003). Carriers of the Asp(298) allele (Asp/Asp or Glu/Asp) were significantly more frequent among the GCA patients than among the controls (P(corr) = 0.0002, odds ratio 3.3, 95% confidence interval 1.7-6.3). The distribution of the 4a/b genotype was similar in GCA patients and controls. No significant associations were found when GCA patients with and without ischemic complications were compared. Our findings show that the Glu/Asp(298) polymorphism of the eNOS gene is associated with GCA susceptibility.Arthritis & Rheumatism 12/2003; 48(11):3219-23. · 7.87 Impact Factor
Top co-authors
Top Journals
Institutions
-
2003–2007
-
Azienda Ospedaliera Santa Maria Nuova di Reggio Emilia
Reggio nell'Emilia, Emilia-Romagna, Italy
-
