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1.
J Crohns Colitis ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243807

RESUMO

BACKGROUND AND AIMS: No consensus exists on optimal strategy to prevent postoperative recurrence (POR) after ileocecal resection (ICR) for Crohn's disease (CD).We compared early medical prophylaxis versus expectant management with treatment driven by findings at elective endoscopy 6-12 months after ICR. METHODS: A retrospective, multicentric, observational study was performed. CD-patients undergoing first ICR were assigned to cohort1 if a biologic or immunomodulator was (re)started prophylactically after ICR, or to cohort2 if no postoperative prophylaxis was given and treatment was started as reaction to elective endoscopic findings. Primary endpoint was rate of endoscopic POR (Rutgeerts>i1). Secondary endpoints were severe endoscopic POR (Rutgeerts i3/i4), clinical POR, surgical POR and treatment burden during follow-up. RESULTS: Of 346 included patients, 47.4% received prophylactic postoperative treatment (proactive/cohort1) and 52.6% did not (reactive/cohort2).Endoscopic POR (Rutgeerts>i1) rate was significantly higher in cohort2 (41.5% vs 53.8%, OR1.81, P=0.039) at endoscopy 6-12 months after surgery. No significant difference in severe endoscopic POR was found (OR1.29, P=0.517). Cohort2 had significantly higher clinical POR rates (17.7% vs 35.7%, OR3.05, P=0.002) and numerically higher surgical recurrence rates (6.7% vs 13.2%, OR2.59, P=0.051). Cox proportional hazards regression analysis showed no significant difference in time to surgical POR of proactive versus expectant/reactive approach (HR2.50, P=0.057). Quasi-Poisson regression revealed a significantly lower treatment burden for immunomodulator use in cohort2 (mean ratio 0.53, P=0.002), but no difference in burden of biologics or combination treatment. CONCLUSIONS: The PORCSE study showed lower rates of endoscopic POR with early postoperative medical treatment compared to expectant management after first ileocecal resection for Crohn's disease.

2.
J Clin Med ; 12(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37048536

RESUMO

Despite the evolution in inflammatory bowel disease (IBD) management during the last 20 years owing to the advent of new advanced therapies, anti-TNF agents still remain the cornerstone of therapy for both Crohn's disease and ulcerative colitis. However, this does not only secure favorable outcomes for patients considering the progressive disease character and the high likelihood of primary or secondary loss of response. Therefore, trying to reach a better treatment approach and maximize the benefits anti-TNF agents offer, optimization strategies should be examined. It has been indicated that optimizing treatment with anti-TNF enhances drug efficacy and has been associated with improved disease outcomes and a complication-free disease course. From this perspective, we aim to provide an overview of currently available data and recent advances in the practices of anti-TNF treatment optimization. Special focus has been given to the role of therapeutic drug monitoring (TDM), as well as the utility of combining anti-TNF with an immunomodulator and the treat-to-target approach.

3.
Cureus ; 15(2): e34655, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36895538

RESUMO

We report a 19-year-old male with congenital, combined deficiency of immunoglobulin (Ig) E and 2/4 subclasses of IgG (G1, G3) and chronic diarrhea. He presented at six years of age with chronic recurrent diarrhea responsive to immunoglobulin treatment. Initially, it was considered of infectious origin. However, at the age of 14 years, ileocolonoscopy and magnetic resonance enterography (MRE) were performed, and they showed a mild, limited, non-specific, terminal ileitis with increased eosinophil count on histology. A diagnosis of possible eosinophilic gastroenteritis was made, and budesonide was administered with temporary relief. However, at the age of 19 years, repeat ileocolonoscopy showed multiple ulcers in the terminal ileum and aphthous ulcers in the cecum, and repeat MRE demonstrated extensive ileal involvement. Esophagogastroduodenoscopy demonstrated the involvement of the upper GI tract with aphthous ulcers. Subsequently, gastric, ileal, and colonic biopsies revealed Ziehl-Neelsen-negative, non-caseating granulomas. We hereby report the first case of IgE and selective IgG1 and IgG3 deficiency complicated with Crohn's disease-like extensive GI involvement.

4.
Eur J Gastroenterol Hepatol ; 35(1): 15-20, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36165073

RESUMO

INTRODUCTION: Smoking has been associated with lower levels of anti-TNF agents, higher antibodies and a reduced response to anti-TNF in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate the possible association between smoking and adverse events (AEs) of biologics in patients with IBD. MATERIAL AND METHODS: Consecutive IBD patients under biologics from a prospective, longitudinal registry of a tertiary center were included. A specially designed questionnaire including a wide range of AEs associated with biologics was also used. RESULTS: A total of 147 patients with IBD under biologics [median age (IQR) 46 (32.5-56) years, Crohn's disease (CD) 109 (74%), female 51 (35%), under combination with immunosuppressants 60 (41 %), under intensified biologic therapy 50 (34%), under anti-TNF 132 (89%), vedolizumab 11 (7.5%), ustekinumab 3 (2%)] who had completed the questionnaire forms for AEs were included. There were 52 (35%) active smokers and 33 (22.5%) ex-smokers. The prevalence of all AEs was 88% in smokers, 87% in ex-smokers and 79% in nonsmokers. Active smoking was significantly associated with the presence of arthralgias and skin rashes ( P = 0.01 and 0.002, respectively). These correlations were the same for the CD and ulcerative colitis (UC), except for arthralgias where there was a significant correlation only with CD ( P = 0.001). There were no significant associations between smoking and other AEs ( P > 0.05). CONCLUSION: Active smoking is associated with the development of dermatological manifestations (both in UC and CD) and arthralgias (in CD) in IBD patients under biologics.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Humanos , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Fator de Necrose Tumoral , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/terapia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Fumar/efeitos adversos , Fumar/epidemiologia , Terapia Biológica , Doença Crônica , Produtos Biológicos/efeitos adversos , Artralgia
5.
Int J Colorectal Dis ; 37(3): 639-646, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35013823

RESUMO

PURPOSE: The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. METHODS: Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. RESULTS: One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. CONCLUSIONS: In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.


Assuntos
Anticorpos Antinucleares , Doenças Inflamatórias Intestinais , Adalimumab/uso terapêutico , Anticorpos Antinucleares/uso terapêutico , Feminino , Humanos , Doenças Inflamatórias Intestinais/complicações , Infliximab/uso terapêutico , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
7.
J Crohns Colitis ; 16(1): 91-97, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34274962

RESUMO

BACKGROUND: Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. METHODS: This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. RESULTS: This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2-59). Crohn's disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6-20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45-5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good's syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18-81]), 21/27 [77%] patients were in clinical remission. CONCLUSION: This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment.


Assuntos
Agamaglobulinemia/complicações , Doenças Inflamatórias Intestinais/etiologia , Adulto , Agamaglobulinemia/epidemiologia , Agamaglobulinemia/terapia , Europa (Continente)/epidemiologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Eur J Gastroenterol Hepatol ; 33(1S Suppl 1): e777-e782, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34284415

RESUMO

AIMS: The home-performed fecal calprotectin (FC) test has been proposed for the remote management of inflammatory bowel disease (IBD) patients. We present our real-world experience on the use of FC home testing in IBD patients under maintenance treatment with adalimumab. METHODS: Consecutive IBD patients on maintenance treatment with adalimumab were studied retrospectively on the basis of prospectively recorded data. FC calprotectin home test (IBDoc, Βühlmann Laboratories AG, Schönenbuch, Switzerland) was analyzed alongside sufficient information on baseline characteristics, follow-up data and treatment modifications, as well as serum biomarkers and endoscopic assessment data on the basis of validated endoscopic scores. RESULTS: From a total of 72 IBD patients under maintenance treatment with adalimumab, 65 (90%) showed compliance with performing the home FC test. FC values were significantly higher in patients who finally needed treatment modification (37%) compared with those who were maintained on stable treatment (63%) (761 µg/g [537-1000] vs. 108 [41-335], P < 0.0001). In the logistic regression analysis FC and erythrocyte sedimentation rate (ESR) were independently correlated with endoscopically active disease (odds ratio: 1.003; 95% confidence interval, 1.001-1.006, P < 0.01 and odds ratio: 1.058; 95% confidence interval, 1.013-1.105, P < 0.05). FC identified patients with endoscopically active disease more effectively than other biomarkers with an area under the receiver operating characteristic curve of 0.78. FC levels >413 µg/g had a sensitivity of 75% and a specificity of 76% in predicting active disease in endoscopy. CONCLUSIONS: These first real-life results indicate that in IBD patients under maintenance treatment with adalimumab FC home test is a valuable tool with high compliance rates that performs better than the other biomarkers in predicting disease endoscopic activity.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Adalimumab/uso terapêutico , Biomarcadores/análise , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colonoscopia , Doença de Crohn/diagnóstico , Endoscopia Gastrointestinal , Fezes/química , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Complexo Antígeno L1 Leucocitário/análise , Estudos Retrospectivos , Índice de Gravidade de Doença
10.
Germs ; 11(1): 105-110, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33898347

RESUMO

INTRODUCTION: Whipple's disease is a rare chronic infectious disease caused by Tropheryma whipplei. The infection mainly affects the small intestine of middle-aged patients, approximately three times more often in males than in females causing malabsorption and excessive weight loss but other organs may be affected as well. CASE REPORT: We describe a case of a 42-year-old woman with a history of chronic diarrhea and weight loss evolving for at least the last 6 years. The diagnosis of Whipple's disease was confirmed by histopathological examination of duodenal biopsy samples with Periodic acid-Schiff positive macrophages and by polymerase chain reaction technique detecting the DNA of Tropheryma whipplei. The patient was commenced on several antimicrobials including beta-lactams and co-trimoxazole but she did not improve. Finally, after-long lasting i.v. tigecycline 100 mg BID she was commenced on p.o. doxycycline along with hydroxychloroquine 200 mg TID for one year and after by p.o. doxycycline alone. DISCUSSION: The intriguing thing with this case was not only the natural resistance to co-trimoxazole but that the infection was controlled empirically with long-lasting i.v. tigecycline since several failed attempts to discontinue i.v. treatment followed. This might be due to erratic absorption of oral drugs due to gut inflammation. CONCLUSIONS: To our knowledge, this is the first case of Whipple's disease successfully treated with long-lasting induction parenteral tigecycline followed by p.o. doxycycline along with hydroxychloroquine for one year and after by p.o. doxycycline alone.

11.
Intest Res ; 19(4): 461-467, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32806874

RESUMO

BACKGROUND/AIMS: The measurement of infliximab trough levels (IFX-TLs) in patients with inflammatory bowel disease (IBD) is performed to optimize treatment. However, the association between the development of adverse events (AEs) and IFX-TLs has not been sufficiently studied thus far. To investigate the possible association of IFX-TLs with AEs in Greek patients with IBD receiving maintenance treatment with IFX. METHODS: A retrospective analysis of the registry data of the Gastroenterology Department of the University Hospital of Heraklion, from IBD patients with at least one available IFX-TL measurement during the years 2016 to 2017 was conducted. AEs reported 4 months before and 4 months after the measured IFX-TLs were recorded. The IFX-TLs of patients with or without AEs were compared. RESULTS: Of a total of 83 IBD patients (61 Crohn's disease [73%]; 52 men [63%]; mean age ± standard deviation, 43.3 ± 16.0 years), 147 measurements of IFX-TLs were available (median 4.69 µg/ mL [1.32-9.16]), and 99 AEs (67.3%, 14 severe) were registered. The median IFX-TL of patients with AEs was 5.79 µg/mL (1.36- 10.25), higher than the median IFX-TL of patients without AEs (3.40 µg/mL [1.30-5.92]), but the difference was not significant (P= 0.97). The presence of infections or dermatologic reactions was not correlated with IFX-TLs. There was no difference in the prevalence of the total AEs (66.7% vs. 73.3%, P= 0.77) or in the analysis of AEs by group between patients with IFX-TLs ≥ 15 µg/ mL and patients with IFX-TLs < 15 µg/mL. CONCLUSIONS: IFX-TLs are not significantly associated with the development of AEs in IBD patients receiving maintenance treatment with IFX.

13.
Eur J Gastroenterol Hepatol ; 31(2): 187-191, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30543573

RESUMO

BACKGROUND: Infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATIs) have been suggested as useful markers for the optimization of treatment in inflammatory bowel disease (IBD). We aimed to estimate the patterns over time of IFX-TLs and ATIs in IBD patients on maintenance treatment with IFX. METHODS: Two different measurements of IFX-TLs and ATIs were performed (ELISA; Eagle BioSciences) at a 10-month interval using serum samples of consecutive patients on maintenance treatment with IFX. Certain biomarkers [hemoglobin, erythrocyte sedimentation rate, C-reactive protein (CRP), platelets, albumin] measured at the same time as well as clinical disease activity and quality of life were assessed. RESULTS: Among a total of 86 IBD patients under maintenance treatment with IFX, 64 [49 Crohn's disease, 15 ulcerative colitis (UC), 42 men, mean age 44.2±15.2 years, 41 in combination therapy with immunomodulator, six in intensified dose], with two available measurements of IFX-TLs and ATIs (A and B), were included in the study. The median levels of IF-TLs were 5.07 (interquartiles range: 1.60-12.73) µg/ml in measurement A and 4.68 (1.19-7.83) µg/ml in measurement B (P<0.0001). Patients whose dose was intensified after the first measurement showed an increase in their median IFX-TLs from 1.47 to 8.5 µg/ml, whereas patients with stable IFX dose showed a significant reduction in the median IFX-TLs from 5.65 to 3.8 µg/ml (P<0.0001). In the logistic regression analysis, the decrease in IFX-TL was correlated significantly and independently with the increase in CRP [odds ratio 5.2 (1.4-19.0), P=0.01]. CONCLUSION: IBD patients on maintenance treatment with IFX show decreasing patterns of IFX-TLs over time associated with increasing patterns of CRP levels.


Assuntos
Anti-Inflamatórios/farmacocinética , Colite Ulcerativa/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/farmacocinética , Infliximab/farmacocinética , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/sangue , Doença de Crohn/diagnóstico , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/sangue , Humanos , Mediadores da Inflamação/sangue , Infliximab/administração & dosagem , Infliximab/sangue , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Resultado do Tratamento
14.
Inflamm Bowel Dis ; 24(6): 1266-1271, 2018 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-29718260

RESUMO

Background: Both muscle-related complaints and elevated serum creatine kinase (CK) levels have been reported in patients with inflammatory bowel disease (IBD) treated with infliximab (IFX), mainly as case reports. The aim of this study was to investigate the effect of IFX therapy on serum CK levels in a cohort of Greek IBD patients. Methods: Demographic, clinical (including muscle complaints), and laboratory data of consecutive IBD patients undergoing IFX treatment and a matched control group of IBD patients without any use of biological treatment were retrospectively analyzed. In both groups, patients having at least 3 CK measurements, with at least 10 days' interval among them, were included. Results: The IFX-treated IBD patient group included 82 individuals (75.6% Crohn's Disease [CD]; mean age, 44.7 ± 13.3 years; 60.9% men; median [interquartile range {IQR}] duration of IFX treatment, 27 [12-84] months). Eighty-two patients without treatment with any biological agent formed the control group (62.2% CD; mean age, 50.4 ± 16.4 years; 59.8% men). Twenty-five IFX-treated patients (30.5%) had elevated mean serum CK levels (>180 U/L), compared with 9 (11%) in the control group (P = 0.0003). The median CK value in the IFX group (123.5 U/L; IQR, 91-190.75) was significantly higher than that of the control group (81 U/L; IQR, 57-112.75; P < 0.0001). In the logistic regression analysis, the presence of hyperCKemia was independently correlated with the use of IFX (odds ratio, 4.03; IQR, 1.64-9.90; P = 0.002). No patient with hyperCKemia in both groups reported any persistent symptom of myopathy. Conclusions: More than 30% of IBD patients on IFX present asymptomatic persistent and treatment-related hyperCKemia. Further relevant prospective investigation is needed. 10.1093/ibd/izy088_video1izy088.video15778459427001.


Assuntos
Creatina Quinase/sangue , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico , Adulto , Idoso , Feminino , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Public Health Nutr ; 19(6): 1081-7, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26223368

RESUMO

OBJECTIVE: The aims of the current report are to present the demographic characteristics, clinical characteristics/biochemical indices and lifestyle habits of the population and to explore the potential association of exclusive olive oil consumption, in relation to lifestyle factors, with coronary artery disease risk. DESIGN: Demographic, lifestyle, dietary and biochemical variables were recorded. Logistic regression analysis was performed in order to estimate the relative risks of developing coronary artery disease. SETTING: The Hellenic study of Interactions between Single nucleotide polymorphisms and Eating in Atherosclerosis Susceptibility (THISEAS), a medical centre-based case-control study conducted in Greek adults. SUBJECTS: We consecutively enrolled 1221 adult patients with coronary artery disease and 1344 adult controls. RESULTS: A higher prevalence of the conventional established risk factors was observed in cases than in controls. Physical activity level was higher in controls (1·4 (sd 0·2) than in cases (1·3 (sd 0·3); P<0·001). Regarding current and ex-smokers, the case group reported almost double the pack-years of the control group (54·6 (sd 42·8) v. 28·3 (sd 26·3), respectively; P<0·001). Exclusive olive oil consumption was associated with 37 % lower likelihood of developing coronary artery disease, even after taking into account adherence to the Mediterranean diet (OR=0·63; 95 % CI 0·42, 0·93; P=0·02). CONCLUSIONS: Exclusive olive oil consumption was associated with lower risk of coronary artery disease, even after adjusting for adoption of an overall healthy dietary pattern such as the Mediterranean diet.


Assuntos
Doença da Artéria Coronariana/prevenção & controle , Azeite de Oliva/administração & dosagem , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta Saudável , Dieta Mediterrânea , Exercício Físico , Feminino , Grécia , Humanos , Estilo de Vida , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Fatores de Risco , Fatores Socioeconômicos , Triglicerídeos/sangue
17.
J Nutr Biochem ; 22(8): 752-7, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21115334

RESUMO

The aim of this study was to investigate the effect of common vitamin D receptor (VDR) gene polymorphisms on the bone mineral density (BMD) of Greek postmenopausal women. Healthy postmenopausal women (n=578) were recruited for the study. The BMD of the lumbar spine and hip was measured using dual-energy X-ray absorptiometry with the Lunar DPX-MD device. Assessment of dietary calcium intake was performed with multiple 24-h recalls. Genotyping was performed for the BsmI, TaqI and Cdx-2 polymorphisms of the VDR gene. The selected polymorphisms were not associated with BMD, osteoporosis or osteoporotic fractures. Stratification by calcium intake revealed that in the low calcium intake group (<680 mg/day), all polymorphisms were associated with the BMD of the lumbar spine (P<.05). After adjustment for potential covariates, BsmI and TaqI polymorphisms were associated with the presence of osteoporosis (P<.05), while the presence of the minor A allele of Cdx-2 polymorphism was associated with a lower spine BMD (P=.025). In the higher calcium intake group (>680 mg/day), no significant differences were observed within the genotypes for all polymorphisms. The VDR gene is shown to affect BMD in women with low calcium intake, while its effect is masked in women with higher calcium intake. This result underlines the significance of adequate calcium intake in postmenopausal women, given that it exerts a positive effect on BMD even in the presence of negative genetic predisposition.


Assuntos
Densidade Óssea/genética , Osteoporose Pós-Menopausa/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Absorciometria de Fóton , Idoso , Alelos , Cálcio da Dieta/administração & dosagem , Estudos Transversais , Feminino , Predisposição Genética para Doença , Genótipo , Grécia , Humanos , Modelos Lineares , Modelos Logísticos , Vértebras Lombares/metabolismo , Vértebras Lombares/patologia , Pessoa de Meia-Idade , Osteoporose/genética , Fraturas por Osteoporose/genética , Pós-Menopausa/genética
18.
BMC Med Genet ; 11: 28, 2010 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-20167083

RESUMO

BACKGROUND: Although plasma fibrinogen levels are related to cardiovascular risk, data regarding the role of fibrinogen genetic variation in myocardial infarction (MI) or coronary artery disease (CAD) etiology remain inconsistent. The purpose of the present study was to investigate the effect of fibrinogen A (FGA), fibrinogen B (FGB) and fibrinogen G (FGG) gene SNPs and haplotypes on susceptibility to CAD in a homogeneous Greek population. METHODS: We genotyped for rs2070022, rs2070016, rs2070006 in FGA gene, the rs7673587, rs1800789, rs1800790, rs1800788, rs1800787, rs4681 and rs4220 in FGB gene and for the rs1118823, rs1800792 and rs2066865 SNPs in FGG gene applying an arrayed primer extension-based genotyping method (APEX-2) in a sample of CAD patients (n = 305) and controls (n = 305). Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), before and after adjustment for potential confounders. RESULTS: None of the FGA and FGG SNPs and FGA, FGB, FGG and FGA-FGG haplotypes was associated with disease occurrence after adjustment. Nevertheless, rs1800787 and rs1800789 SNPs in FGB gene seem to decrease the risk of CAD, even after adjustment for potential confounders (OR = 0.42, 95%CI: 0.19-0.90, p = 0.026 and OR = 0.44, 95%CI:0.21-0.94, p = 0.039, respectively). CONCLUSIONS: FGA and FGG SNPs as well as FGA, FGB, FGG and FGA-FGG haplotypes do not seem to be important contributors to CAD occurrence in our sample. On the contrary, FGB rs1800787 and rs1800789 SNPs seem to confer protection to disease onset lowering the risk by about 50% in homozygotes for the minor alleles.


Assuntos
Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/prevenção & controle , Fibrinogênio/genética , Variação Genética , Polimorfismo de Nucleotídeo Único , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/genética , Síndrome Coronariana Aguda/prevenção & controle , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Feminino , Frequência do Gene , Genes Recessivos , Grécia , Haplótipos , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Razão de Chances , Fatores de Risco
19.
J Nutr Biochem ; 21(10): 1008-14, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19962295

RESUMO

Metallothioneins (MT), the antioxidant zinc-binding proteins, seem to mediate cardioprotection. It has been postulated that zinc homeostasis and MT function may be altered, as a consequence of oxidative stress, in cardiovascular disease (CVD), with a potential implication of MT genetic polymorphisms. The present study explores the role of +647A/C and +1245A/G MT1A polymorphisms on the susceptibility to CVD, zinc status and enzyme antioxidant activity, in the Greek and Italian populations. The country selection was based on the lower zinc status and the reduced zinc dietary intake in Greece than in Italy despite the similar Mediterranean dietary pattern. A total of 464 old, healthy control subjects and 369 old CVD patients more than 70 years of age were studied. Logistic regression model indicated that +1245 MT1A G+ genotype significantly increased the risk of CVD in Greece (34.4% vs. 23.2%; odds ratio=1.88, 95% confidence interval=1.14-3.08; P=.013) but not in Italy. Haplotype analysis showed an increment of CG haplotype frequency in CVD Greek patients (17.4% vs. 10.6%, P<.05). Differential country-related frequency distribution was also recorded. Applying a multivariate regression model, +647/+1245 MT1A haplotype was associated with a modulation of enzyme antioxidant activities in both countries. Decreased plasma zinc and reduced intracellular Zn release, as well as increased enzyme antioxidant activity, were more apparent in Greek healthy donors than in Italy. In conclusion, +1245 MT1A polymorphism and +647/+1245 MT1A haplotype are implicated in CVD in Greece but not in Italy, suggesting a role of gene-diet interaction in the disease predisposition.


Assuntos
Doenças Cardiovasculares/genética , Haplótipos , Metalotioneína/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Catalase/sangue , Estudos de Coortes , Feminino , Citometria de Fluxo , Glutationa Peroxidase/sangue , Grécia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Superóxido Dismutase/sangue
20.
Clin Chem Lab Med ; 47(12): 1471-3, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19863298

RESUMO

BACKGROUND: Rs619203 (Cys2229Ser) and rs529038 (Asp2213Asn) polymorphisms in the ROS1 gene have been studied in relation to myocardial infarction (MI) yielding inconsistent results. We investigated the role of ROS1 rs529038 polymorphism in coronary artery disease (CAD) in Greeks using a case-control study. METHODS: Genotyping for rs529038 polymorphism was performed using a multiplex PCR technique in patients with CAD (n=294) and controls (n=311). Logistic regression analysis was used to calculate crude and adjusted odds ratios (ORs). RESULTS: Logistic regression analysis did not show any statistically significant effect of ROS1 polymorphism in the occurrence of CAD (AG vs. AA, OR: 1.08, p=0.635; GG vs. AA, OR: 0.62, p=0.220). Adjustment for confounding factors gave similar results, irrespective of the type of disease (i.e., stable coronary artery disease vs. acute coronary syndrome). CONCLUSIONS: Our findings do not support the hypothesis that ROS1 rs529038 polymorphism is an important contributing factor in the etiology of CAD in the Greek population.


Assuntos
Asparagina/genética , Ácido Aspártico/genética , Infarto do Miocárdio/genética , Polimorfismo Genético , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética , Idoso , Estudos de Casos e Controles , Feminino , Grécia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Tirosina Quinases/química , Proteínas Proto-Oncogênicas/química
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