RESUMO
We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. INTRODUCTION: This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. METHODS: Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. RESULTS: At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m2, and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p < 0.01) and of 5.9 ng/ml for rs10741657 (p = 0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. CONCLUSION: This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.
Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Polimorfismo de Nucleotídeo Único , Deficiência de Vitamina D/genética , Vitamina D/análogos & derivados , Idoso , Colecalciferol/uso terapêutico , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Estações do Ano , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológicoRESUMO
PURPOSE: The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy. METHODS: A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients. RESULTS: The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity. CONCLUSIONS: This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Citocromo P-450 CYP2B6/genética , Polimorfismo Genético , Adulto , Alelos , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Mama/efeitos dos fármacos , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citocromo P-450 CYP2B6/metabolismo , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Líbano , Pessoa de Meia-Idade , Mielopoese/efeitos dos fármacos , Gradação de Tumores , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Análise de SobrevidaRESUMO
A study was conducted to determine risk factors associated with brucellosis infection in an outbreak in Chouf district of Lebanon during summer 2009. Cases of brucellosis reported to the Ministry of Public Health were identified, and for each case 2 controls were matched by sex, age and residence. Sociodemographic data, exposure to animals and animal products, knowledge about brucellosis, symptoms and history of past brucellosis infections were collected. Consumption of raw cheese was a significant risk factor for contracting brucellosis (matched OR = 29.5), whereas wearing gloves when in contact with animals and animal products and self-preparing dairy products were protective factors (OR = 0.08 and 0.13 respectively). Low and inaccurate knowledge about brucellosis was prevalent among subjects, with a common misconception about human-human transmission. Ensuring animal vaccination, educating people on correct ways of milk pasteurization and handling meat products, and elevating food safety monitoring threshold are key elements in controlling brucellosis.
Assuntos
Brucelose/epidemiologia , Laticínios/microbiologia , Surtos de Doenças , Conhecimentos, Atitudes e Prática em Saúde , Pasteurização/normas , Adolescente , Adulto , Idoso , Animais , Brucelose/etiologia , Brucelose/prevenção & controle , Estudos de Casos e Controles , Criança , Pré-Escolar , Laticínios/efeitos adversos , Feminino , Inocuidade dos Alimentos/métodos , Humanos , Líbano/epidemiologia , Masculino , Carne/efeitos adversos , Carne/microbiologia , Carne/normas , Pessoa de Meia-Idade , Pasteurização/métodos , Fatores de Risco , Inquéritos e Questionários , Vacinação , Adulto JovemRESUMO
Solute carrier family 22 member 5 (SLC22A5) encodes a sodium-dependent ion transporter responsible for shuffling carnitine across the plasma membrane. This process provides energy for the heart, among other organs allowing beta-oxidation of fatty acids. Mutations in SLC22A5 result in primary carnitine deficiency (PCD), a disorder that manifests with cardiac, skeletal, or metabolic symptoms. We hereby describe two novel mutations in SLC22A5 in two Lebanese families associated exclusively with a cardiac phenotype. The frequency of the cardiac, metabolic and skeletal symptoms in PCD patients remains undefined. All the reported eight PCD patients belonging to five different Lebanese families have an exclusive cardiac phenotype. Carnitine levels appear to be directly linked to the type and position of the mutation and the severity of the phenotypic presentation does not seem to be associated with serum carnitine levels. A comprehensive review of 61 literature-reported PCD cases revealed an exclusive cardiac manifestation frequency at 62.3% with a very low likelihood of simultaneous occurrence of cardiac and metabolic manifestation.
Assuntos
Cardiomiopatias/genética , Cardiomiopatia Dilatada/genética , Carnitina/deficiência , Hiperamonemia/genética , Doenças Musculares/genética , Miocárdio/patologia , Proteínas de Transporte de Cátions Orgânicos/genética , Fenótipo , Sequência de Bases , Cardiomiopatias/patologia , Cardiomiopatia Dilatada/patologia , Carnitina/genética , Criança , Pré-Escolar , Códon sem Sentido/genética , Primers do DNA/genética , Ecocardiografia , Feminino , Humanos , Hiperamonemia/patologia , Lactente , Líbano , Modelos Logísticos , Masculino , Dados de Sequência Molecular , Doenças Musculares/patologia , Razão de Chances , Linhagem , Reação em Cadeia da Polimerase , Análise de Sequência de DNA , Deleção de Sequência/genética , Membro 5 da Família 22 de Carreadores de SolutoRESUMO
A study was conducted to determine risk factors associated with brucellosis infection in an outbreak in Chouf district of Lebanon during summer 2009.Cases of brucellosis reported to the Ministry of Public Health were identified, and for each case 2 controls were matched by sex, age and residence.Sociodemographic data, exposure to animals and animal products, knowledge about brucellosis, symptoms and history of past brucellosis infections were collected.Consumption of raw cheese was a significant risk factor for contracting brucellosis [matched OR = 29.5], whereas wearing gloves when in contact with animals and animal products and self-preparing dairy products were protective factors [OR = 0.08 and 0.13 respectively]. Low and inaccurate knowledge about brucellosis was prevalent among subjects, with a common misconception about human-human transmission.Ensuring animal vaccination, educating people on correct ways of milk pasteurization and handling meat products, and elevating food safety monitoring threshold are key elements in controlling brucellosis
أجرى الباحثون الدراسة للتعرف على عوامل الاختطار المرافقة للعدوى بالبروسيلات في سياق فاشية اندلعت في منطقة الشوف في لبنان خلال صيف عام 2009 . فقد حدد الباحثون الحالات التي أبلغت وزارة الصحة العامة بها، وفي مقابل كل حالة أخذوا شاهدين متوافقين بالجنس والعمر وموقع السكن، وجمعوا بيانات اجتماعية وديموغرافية وبيانات حول التعرض للحيوانات ومنتجات الحيوانات، والمعارف حول داء البروسيلات، والأعراض وتاريخ العدوى السابقة بالبروسيلات، واتضح أن استهلاك الجبن الخام هو عامل اختطار يعتد بأهميته في العدوى بالبروسيلات [معدل الأرجحية الموافق 29.5]، وأن ارتداء القفازات حين مخالطة الحيوانات ومنتجاتها [معدل الأرجحية 0.08]مع التحضير الذاتي لمنتجات الألبان من العوامل الواقية [معدل الأرجحية 0.13]. واتضح أن نقص المعارف وتوافر المعارف غير الصحيحة عن داء البروسيلات ينتشران بين المصابين، مع شيوع مفاهيم خاطئة حول السراية من إنسان لآخر. أما العناصر الهامة في مكافحة داء البروسيلات فهي ضمان تلقيح الحيوانات وتثقيف الناس حول الطرق الصحيحة لبسترة اللبن وإعداد منتجات اللحوم، ورفع مستوى عتبة رصد سلامة الغذاء
Une étude a été menée afin de déterminer les facteurs de risque associés à la brucellose au cours d'une flambée dans le district de Chouf [Liban]pendant l'été 2009.Des cas de brucellose notifies au ministère de la Santé publique ont été identifiés, et pour chaque cas deux témoins ont été appariés pour l'âge, le sexe et le lieu de résidence.Les données sociodémographiques, les antécédents d'exposition aux animaux et aux produits destinés aux animaux, les connaissances sur la brucellose, les symptômes et les antécédents de brucellose ont été recueillis.La consommation de fromage cru était un facteur de risque important pour l'infection [OR apparié = 29, 5]tandis que le port de gants lors des contacts avec des animaux et des produits destinés aux animaux ainsi que la préparation des produits laitiers par la personne elle-même étaient des facteurs protecteurs [OR = 0, 08 et 0, 13 respectivement]. Des connaissances faibles et inexactes sur la brucellose étaient prévalences chez les patients, et les idées fausses sur la transmission interhumaine étaient courantes.Assurer une vaccination animale, éduquer la population en ce qui concerne les bonnes méthodes de pasteurisation du lait et de manipulation des produits carnés, et relever les niveaux de suivi de la sécurité sanitaire des aliments sont des éléments des de la lutte contre la brucellose