Protein Z G79A and A-13G gene polymorphisms in Italian patients with Behçet's disease.

OBJECTIVE: To investigate potential associations between A-13G and G79A polymorphisms of the protein Z gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD). METHODS: 176 Italian patients who satisfied the International Study Group criteria for BD and 134 healthy age- and sex- matched blood donors were genotyped for A-13G and G79A polymorphisms of the protein Z gene by molecular methods. 113 and 112 of the 176 BD patients were also genotyped for factor V Leiden and prothrombin gene G20210A polymorphisms. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of A-13G and G79A polymorphisms did not differ significantly between BD patients and healthy controls.The frequencies of carriage rates of protein Z G79A and A-13G polymorphisms in BD patients with and without DVT were similar. Similarly, no associations between thrombotic events and the protein Z gene polymorphisms studied were observed in BD patients carrying factor V Leiden or prothrombin gene G20210A mutations. No significant associations were observed between protein Z polymorphisms and the occurrence of specific clinical findings. CONCLUSION: No association between DVT and A-13G or G79A polymorphisms of the protein Z gene was found in Italian BD patients. Furthermore, these protein Z polymorphisms in BD do not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations.

Toll-like receptor 4 (TLR4) gene polymorphisms in Italian patients with Behçet's disease.

OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, clinical features, and severity of Behçet's disease (BD). METHODS: A total of 189 Italian patients who satisfied the International Study Group criteria for BD and 210 healthy age- and sex-matched blood donors were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. Severity score was calculated. RESULTS: The distribution of allele and genotype frequencies did not differ significantly between the BD patients and the healthy controls. No significant associations were found when BD patients with and those without clinical manifestations were compared. No association between TLR4 polymorphisms and severity score was observed. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, clinical expression of, and severity of BD in Italian patients.

Toll-like receptor 4 (TLR4) gene polymorphisms in giant cell arteritis.

OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 155 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 210 population-based controls from the same geographical area were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of allele and genotype frequencies did not differ significantly between GCA patients and healthy controls. Carriers of the -299 G allele (G/A+ G/G) [odds ratio (OR) 1.78, 95% confidence intervals (CI) 0.90-3.50)] were more frequent among GCA patients than among the controls, but the difference was not statistically significant. No significant associations were found when GCA patients with and without PMR or with and without severe ischemic complications were compared. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, and clinical expression of, GCA in Italian patients.

-463 G/A myeloperoxidase promoter polymorphism in giant cell arteritis.

OBJECTIVE: To investigate potential associations between-463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 156 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 235 population-based controls from the same geographic area were genotyped for-463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischaemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of the MPO-G/A genotype differed significantly between patients with GCA and the controls (p(corr) = 0.003). Allele G was significantly more frequent in patients with GCA than in the controls (p(corr) = 0.0002, OR 2.0, 95% CI 1.4 to 2.9). Homozygosity for the G allele was significantly more frequent in patients with GCA than in controls (p(corr) = 0.0002, OR 2.2, 95% CI 1.4 to 3.4). No significant associations were found when patients with GCA with and without polymyalgia rheumatica or with and without severe ischaemic complications were compared. CONCLUSIONS: Our findings show that the-463 G/A promoter polymorphism of the MPO gene is associated with GCA susceptibility and support a role for MPO in the pathophysiology of GCA.

Lack of association of the -463 G/A myeloperoxidase promoter polymorphism with Behcet's disease in Italian patients.

OBJECTIVE: To investigate potential associations between the -463 G/A myeloperoxidase (MPO) promoter polymorphism and susceptibility to, and clinical expression of, Behçet's disease (BD). METHODS: One hundred and seventy-five Italian patients who satisfied the International Study Group criteria for BD and 235 healthy age- and sex-matched blood donors were genotyped for the -463 G/A promoter polymorphism of the MPO gene by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of the MPO -463A/G polymorphism did not differ significantly between the BD patients and the healthy controls. Carriers of the -463 A allele (A/A or A/G) [odds ratio (OR) 0.7, 95% confidence interval (CI) 0.5-1.1] and homozygosity for A allele (OR 0.3, 95% CI 0.1-1.3) were less frequent among BD patients than among the controls, but the difference was not statistically significant. No significant associations were found when BD patients with and those without clinical manifestations were compared. CONCLUSION: Our data suggest that the -463 G/A promoter polymorphism of the MPO gene is not associated with susceptibility to, and clinical expression of, BD in Italian patients.

The codon 72 polymorphic variants of p53 in Italian rheumatoid arthritis patients.

OBJECTIVE: The p53 tumor suppressor protein plays an important role in cell apoptosis. The wild type p53 protein presents a common polymorphism at position 72 resulting in either a proline or an arginine residue at this position, leading to differences between the two variants in the induction of apoptosis. We examined the possible associations of this polymorphism with the occurrence of rheumatoid arthritis (RA) and its severity in a series of RA patients of Italian origin. METHODS: 170 consecutive RA patients fulfilling the 1997 ACR criteria and seen over a 4-month period in our rheumatology centre were studied. The medical records of the patients were reviewed for demographic and clinical parameters. Radiographs of the hands and feet taken at disease onset and after 5 years were available for 122 of the patients and were used to determine the presence and number of erosions, which were scored according to the modified Sharp/van der Heijde method (S/vdH). All of the RA patients and controls were genotyped by the polymerase chain reaction and allele-specific oligonucleotide techniques for p53 gene polymorphism Arg/Pro at codon 72. RESULTS: The distribution of the polymorphism of Arg/Pro 72 did not differ significantly between patients and healthy controls (Arg/Arg 47.1 vs 48.5%, Arg/Pro 43.5% vs 42%, Pro/Pro 9.8 vs 9.5% respectively, p=ns). Patients carrying the Pro/Pro genotype had a significantly higher percentage of erosive disease at year 5 compared with patients carrying the Arg/Arg genotype (Pro/Pro 93%, Arg/Arg 52%, p=0.0001). The mean number of eroded joints per patient at 5 years was higher in the Pro/Pro subgroup and significantly lower in the Arg/Arg subgroup (Pro/Pro 13.2, Arg/Arg 3.6, p=0.0001). The mean S/vdH erosive score, joint space narrowing score and total damage score were significantly higher in the Pro/Pro subgroup compared with the Arg/Arg and Arg/Pro subgroups. CONCLUSION: In the Italian population there is no association between codon 72-p53 gene polymorphism and the occurrence of RA. However, this polymorphism is associated with the structural damage of the disease.

Isolation of Bartonella henselae from domestic cats in an Italian urban area.

Bartonella henselae is the causative agent of Cat Scratch Disease (CSD) in humans. Cat is considered the reservoir of the bacterium. Identification of bacteriemic cats is the basic tool in the prophylaxis of CSD. Blood samples were collected between January 1999-December 2000 from 248 domestic cats living in an urban area (Reggio Emilia) in Northern Italy and tested for Bartonella henselae bacteriemia. Cultural and PCR methods were used. PCR was used directly on cat blood as well as to identify the Bartonella strain growth in culture. 24 (9.7 %) cats were found bacteriemic, most of which aged <1 year. A higher sensitivity was demonstrated by cultural method compared with PCR.

Molecular characterization of first human Bartonella strain isolated in Italy.

The aim of this study was to characterize a Bartonella strain (BA-1) isolated from a blood culture of an Italian, human immunodeficiency virus-positive patient with bacillary angiomatosis. We analyzed the isolate using molecular biology methods such as whole-cell fatty acid analysis, PCR-restriction fragment length polymorphism analysis, type-specific 16S rRNA PCRs, sequence analysis of the 16S rRNA, pulsed-field gel electrophoresis, and arbitrarily primed PCR. The BA-1 isolate turned out to be a Bartonella quintana strain, similar but not identical to B. quintana Oklahoma, which was used as a control strain.

Intercellular adhesion molecule-1 gene polymorphisms in Behçet's Disease.

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is strongly expressed in vascular endothelial cells and perivascular inflammatory infiltrates in immunopathologic studies of Behçet's disease (BD) lesions. ICAM-1 genes may contribute to the inflammatory events responsible for the vessel damage in BD. We examined potential associations of ICAM-1 gene polymorphisms with BD susceptibility. METHODS: Case patients were 74 consecutive Italian patients with BD who were followed at the Bologna, Ferrara, Milano, Potenza, Prato, Reggio Emilia, and Trento rheumatology, ophthalmology, and neurology units over a 3 year period (1997-99) who satisfied the International Study Group criteria for BD; 228 healthy Italian blood donors from the same geographic areas were selected as control groups. All BD patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in BD patients than in controls (20.3% vs 5.7%; p = 0.001, pcorr = 0.002, OR 4.2, 95% CI 1.9-9.3). The distribution of E/K 469 genotype was similar in patients and controls. Comparing patients with different clinical features, we found only a trend to higher frequency of R241 in patients with articular manifestations (21.4% vs 12.5%; p = 0.08). CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with BD susceptibility.

Intercellular adhesion molecule 1 (ICAM-1) gene polymorphisms in Italian patients with rheumatoid arthritis.

AIMS: Rheumatoid arthritis (RA) has a wide range of clinical expressions which probably reflects different genetic backgrounds. Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the inflammatory synovial activity in RA. The aim of this study was to examine the potential associations of ICAM-1 gene polymorphisms with RA and its severity. METHODS: Seventy-eight seropositive Italian RA patients with erosive disease entered the study. Radiographs of hands and feet 5 years after the diagnosis were available for 68 patients and were evaluated for the number of eroded joints. We obtained an erosive score for each patient by counting the number of joints with at least one erosion. Patients in the upper part of the distribution over the median were considered as fast eroders (FE) and the others as slow eroders (SE). Patients' records were also evaluated for the presence of extra-articular features. 228 healthy subjects of the same ethnic origin were selected as a control group. All of the RA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphisms G/R at codon 241 (exon 4) and E/K at codon 469 (exon 6). RESULTS: The carriage rate of allele R241 was significantly higher in RA patients than in healthy controls (12.8% versus 5.7%, p = 0.039; odds ratio: 2.4 [95% CI 1.02 to 5.79]). The allele frequencies and carriage rate of the E 469 gene did not differ significantly between RA patients and the control group. When we compared the control group with the patients with more or less severe disease (presence or absence of extra-articular features, SE and FE) we found that only the group of patients with the more favourable course maintained a significant difference in the carriage rate of R241 (16.7 vs 5.7%, p = 0.009 for patients without extra-articular features and 18.9 vs 5.7%, p = 0.004 for SE patients). CONCLUSION: Our preliminary findings show that G/R 241 polymorphism of ICAM-1 is associated with RA, and that this confers a reduced risk of extra-articular manifestations and is associated with a slow rate of joint destruction.

Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity.

OBJECTIVE: Intercellular adhesion molecule 1 (ICAM-1) is widely distributed in shoulder synovial membrane of active polymyalgia rheumatica (PMR) and strongly expressed in granulomatous inflammatory infiltrate of the temporal artery in giant cell arteritis (GCA). ICAM-1 genes may contribute to the inflammatory PMR/GCA processes. We examined potential associations of ICAM-1 gene polymorphisms with PMR/GCA susceptibility and severity. METHODS: We enrolled 121 consecutive patients with "pure" PMR and 56 patients with biopsy positive GCA residing in Reggio Emilia, Italy. Among patients with PMR, 91 had a followup duration of at least one year. Selected as control subjects were 228 healthy blood donors, 75 patients with nonarteritic central retinal artery occlusion, and 116 cataract surgery patients from the same geographic area. All PMR/GCA patients and controls were genotyped by polymerase chain reaction and allele-specific oligonucleotide techniques for ICAM-1 polymorphism at codon 241 (exon 4) and codon 469 (exon 6). RESULTS: The frequency of R241 was significantly higher in PMR/GCA patients [p = 0.00001, odds ratio (OR) 5.0 (95% confidence intervals, CI 2.6-9.6) ], in pure PMR patients [p = 0.00001, OR 5.0 (95% CI 2.5-10.0)], and in GCA patients [p = 0.00005; OR 5.0 (95% CI 2.2-11.5)] compared to the healthy controls. The frequency of R241 was significantly higher in total PMR/GCA patients compared to patients with nonarteritic central retinal artery occlusion [p = 0.0007; OR 5.3 (95% CI 1.8-15.5)] and cataract surgery patients [p = 0.0003; OR 4.1 (95% CI 1.8-9.0)]. The distribution of E/K 469 genotype was similar in PMR/GCA patients and in the 3 control groups. Cox proportional hazards modeling identified 2 variables that independently increased the risk of PMR relapse/recurrence: erythrocyte sedimentation rate at diagnosis > 72 mm/h [relative risk 1.6 (95% CI 1.1-2.3)] and the presence of R241 allele [relative risk 1.6 (95% CI 1.1-2.4)]. CONCLUSION: Our findings show that G/R 241 polymorphism of ICAM-1 is associated with PMR/GCA susceptibility and confers an increased risk of relapse/recurrence in PMR.