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1.
Ann Med Surg (Lond) ; 86(6): 3222-3226, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38846846

RESUMO

Introduction: Vitamin D is a liposoluble steroid hormone that plays a crucial role in the maintenance of bone metabolism and calcium homoeostasis. Many studies on the effects of vitamin D on general health have been significantly increased, driven by new findings concerning the systemic and extraskeletal effects of this hormone. This study was performed to determine whether low levels of vitamin D were associated with hypertension in Syrian people. Materials and methods: This retrospective cohort study consisted of 207 subjects, including 83 (40.1%) patients suffering from essential hypertension and 124 (59.9%) patients with normal blood pressure. Aged older than 18 years, who was referred to the endocrinology clinic from September 2022 to September 2023. The data were analysed by using SPSS (version 25). Logistic regression analyses were performed with adjustments for age, sex, and waist circumference. Results: Hypertension rates were 73%, 20%, and 5% in 25-hydroxyvitamin D groups less than 12 ng/ml, 12-20 ng/mL, and greater than or equal to 20 ng/ml, respectively. Odds ratios (95% CIs) for hypertension adjusting for age, sex, and waist circumference were 178.6 (30.5_1045.6), 5.13 (0.9_26.5) for 25-hydroxyvitamin D levels less than 12 ng/ml, and 12-20 ng/ml, respectively, compared with the greater than or equal to 20 ng/ml group. Conclusions: This study has shown a high prevalence of low vitamin D levels (25OHVD/20 ng/ml) among a sample of Syrian people (78.3%). The lowest 25OHVD group was associated with a higher prevalence of hypertension, which refers to an adverse association between vitamin D level and essential hypertension. Further research is needed to confirm this relationship.

2.
Medicine (Baltimore) ; 103(4): e36107, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38277548

RESUMO

The present study aimed to investigate the occurrence of autoimmune thyroid disease (AITD) in patients with type 1 diabetes mellitus (T1DM) by the presence of antithyroid peroxidase (anti-TPO Ab). Furthermore, we studied the relationship of clinical and thyroid ultrasound (US) characteristics with anti-TPO Ab. This cross-sectional study was performed in Al- Mowasat and Al-Assad University Hospitals from 2021 to 2023. Clinical, laboratories, and US features were collected and analyzed between positive compared to negative anti-TPO Ab. Of 76 patients, anti-TPO Ab was positive in 12 patients (15.7%) with female predominance [n = 10 (83.3%)]. Gender showed a difference between anti-TPO Ab groups (P = .026). DM duration showed a difference (P = .034), which was dominant for a group of positive anti-TPO Ab (median = 9). The age at DM diagnosis also showed a difference (P = .048), where most patients were under 10- years old at diagnosis [n = 39 (51.3%)] and the highest number of anti-TPO Ab positive patients [n = 7 (58.3%)] were in this age category. US findings showed a significant difference (P = .001). Regarding positive anti-TPO Ab patients, the most frequent US finding was immune pattern [7 (58.3%)], which was more common than in the negative group (12.5%). Age, hemoglobin A1c (HBA1c), and body mass index (BMI) did not present differences (P = .391, 0.692, and 0.453, respectively), however, all anti-TPO Ab positive patients were older than ten years and had HBA1c more than 8. Thyroid-stimulating hormone (TSH) was abnormal in 2 patients (16.6%) and both in anti-TPO Ab positive group. This study suggests that anti-TPO Ab appears in older patients and with longer MD duration. Also, data support using US and anti-TPO Ab as earlier markers for AITDs, and further recommending regular annual monitoring by US and anti-TPO Ab in all patients with T1DM for AITDs diagnosis, especially in females.


Assuntos
Diabetes Mellitus Tipo 1 , Doença de Hashimoto , Humanos , Feminino , Idoso , Criança , Masculino , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Estudos Transversais , Autoanticorpos , Síria , Hemoglobinas Glicadas , Peroxidase
3.
Medicine (Baltimore) ; 102(37): e34959, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713906

RESUMO

We proceeded with this study to investigate the relationship between hypothyroidism and lipid profile disturbance. A cross-sectional study at Al- Mowasat University Hospital in Damascus was conducted from March 2021 to March 2022, and included 324 adults. For each participant with abnormal thyroid stimulating hormone (TSH), free thyroxine (FT4) was requested. The participants were categorized into 3 groups: euthyroid (226 participants), subclinical hypothyroidism (SCH) (75 participants), and overt hypothyroidism (23 participants). Fasting lipid profile was tested as: cholesterol (Chol), triglycerides (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL). A significant relationship between hypothyroidism and dyslipidemia was noticed. LDL, TG, and Chol but not HDL showed a significant difference between study groups (euthyroidism, subclinical, and overt hypothyroidism). The lowest levels of these parameters were in euthyroidism and increased in subclinical and overt hypothyroidism subsequently. Overt hypothyroidism showed a significant difference in LDL, TG, and Chol compared to euthyroidism, however, we did not find a difference in lipid parameters in SCH compared to euthyroidism. LDL and Chol showed significant differences between subclinical and overt hypothyroidism. TSH had a positive weak correlation with LDL, TG, and Chol, however, there was no correlation with HDL. Also, FT4 had a negative weak correlation with LDL, TG, and Chol, however, there was a positive correlation with HDL. Our findings suggest a higher level of lipids (LDL, TG, and Chol) among SCH and overt hypothyroidism compared to general population. A weak correlations of lipid parameters with TSH and FT4 were detected. It is not well evident whether a restoration of euthyroidism might influence the morbidity and mortality, especially cardiovascular comorbidities, in this population, which mandates future studies.


Assuntos
Hipotireoidismo , Adulto , Humanos , Estudos Transversais , Síria , Hipotireoidismo/epidemiologia , Triglicerídeos , Lipoproteínas HDL , Tireotropina
4.
Ann Med Surg (Lond) ; 85(4): 670-675, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37113956

RESUMO

Thyroid disorders were reported to be associated with various diseases, particularly dyslipidemia. This study aimed to assess the prevalence of thyroid disorders in a group of apparently healthy Syrians and investigate the relationship between subclinical hypothyroidism and metabolic syndrome (MetS). Methods: A retrospective, cross-sectional study was performed at Al-Assad University Hospital. Participants were healthy individuals aged 18 years and older. Data about their biochemical tests, weight, height, BMI, and blood pressure were collected and analyzed. Participants were categorized according to their thyroid tests into euthyroid, subclinical hypothyroid, subclinical hyperthyroid, and according to their BMI into normal, overweight, and obese, and according to the International Diabetes Foundation into normal and having MetS. Results: A total of 1111 participants were involved in this study. Subclinical hypothyroidism and subclinical hyperthyroidism were found in 4.4 and 1.2% of participants, respectively. The incidence of subclinical hypothyroidism was significantly increased in females and in the presence of positive antithyroid peroxidase. Subclinical hypothyroidism was significantly associated with MetS, a higher waist circumference, central obesity, and triglycerides; however, there was no correlation with high-density lipoprotein. Conclusion: The prevalence of thyroid disorders among Syrians was consistent with the results of other studies. These disorders were significantly more common in females compared to males. Add to that, subclinical hypothyroidism was significantly associated with MetS. Since MetS is a known factor for morbidity and mortality, this may raise the attention needed to perform future prospective trials to evaluate the possible benefits of subclinical hypothyroidism treatment with a low dose of thyroxin.

5.
Diabetes Ther ; 13(9): 1573-1583, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35821495

RESUMO

INTRODUCTION: Prediabetes is a major risk factor for diabetes and many chronic complications, particularly cardiovascular disease (CVD). Risk factors vary among races and demographics. This is the first study to assess prediabetes in Syria and its relevant risk factors. METHODS: This cross-sectional study was conducted in a primary health clinic in Al-Mouwasat University Hospital, the major Hospital in Damascus, Syria. Interviews, examinations, and blood investigations were carried out by qualified physicians in the clinic. RESULTS: This study included 406 participants, of which 363 (89.4%) were females, 43(10.6%) were males, 91 (22.4%) had prediabetes, 108 (26.6%) were overweight, and 231 (56.9%) were obese. Older age, positive family history of diabetes, obesity, abdominal obesity in females, high cholesterol, being married, and CVD were statistically significantly associated with prediabetes (p < 0.05). However, prediabetes was not associated with gender, living in the city or country, cigarette smoking, hypertension, diet, triglycerides, or polycystic ovary syndrome (p > 0.05). However, in the multivariable analysis, only high cholesterol, familial diabetes, and waist diameter had significant association. CONCLUSIONS: Prevalence of prediabetes in our study in Syria was higher than what was estimated by previous studies. While many risk factors were similar to other countries in the regions, other risk factors differed. These results were highly reflective of high burden of prediabetes and diabetes, mainly in relatively young females. Further studies are required to tackle this rising issue as it imposes major complications in the long term, and the high financial burden on the health care system.

6.
Heliyon ; 8(5): e09451, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35620616

RESUMO

Syrian eating habits are trending towards westernized patterns that are high in carbohydrates, fats, and meat. This accompanied by an increasingly sedentary lifestyle has affected young adults' dietary habits. As a consequence, obesity and overweight young adults are significantly increasing in prevalence. This study aims to assess the pattern of eating habits and their relation with psychosocial factors among university students. A cross-sectional study was conducted among Syrian Private University students using a self-administrated questionnaire. The questionnaire consisted of 3 sections: socio-demographic characteristics, eating habits, and psychosocial factors. Each item from the eating habits questionnaire was scored "1" if the response was healthy or "0" if the response was unhealthy. All items were summed and the total score was obtained for each student. Students' scores were summed and divided by the total number of students to deduce the total mean of eating habits. Hierarchical multivariate linear regression was used to evaluate factors associated significantly with eating habit score and psychological factors. Of 728 students included in the study 398 (54.7%) were females. Overweight and obese participants represented 154 (21.4%) and 49 (6.8%) respectively. Around 316 (43.4%) were smokers and 135 (18.5%) drank alcohol. Only 259 (36.0%) students reported they adopted healthy eating habits. Of them, 233 (32%) and 306 (42%) ate meals and breakfast regularly respectively. Participants' had a moderate eating habits score; the mean total was 5.96 (SD ± 1.95). Multivariate analysis revealed that non-smokers (p < 0.001), exercising (p = 0.002), living with family (p < 0.001), and eating because of feeling happy (p = 0.014) were factors significantly associated with eating habits score and psychological factors. While R2 adjusted were 0.109 and 0.117 in the first and second model, the total model accounted for 13.2% of variance. Half of the students demonstrated unhealthy eating habits. The identified socio-demographic and psychological factors were significantly affecting students' eating habits. These findings can be used to provide targeted lifestyle modification advice via health promotion programs towards these specific groups.

7.
Ann Med Surg (Lond) ; 76: 103457, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35308427

RESUMO

Background: This study aims to identify the prevalence of 25OHD deficiency in Syrian patients and investigate the relationship with obesity and lipid profile. Methods: A retrospective cohort study consisted of 201 patients of age >10 years, who referred to Al Assad and Al Mouwasat University Hospitals, Damascus, Syria from Oct/2020 to Oct/2021. The data was analyzed by using linear regressions and produced a matrix of correlations with significant equations between study variables. Results: Firstly, participants were divided depending on 25OHD levels, where 92.5% of patients had 25OHD <30 ng/mL. Inverse correlation between 25OHD and BMI (P ≤ 0.001) was observed, where severe 25OHD deficiency group had higher BMI (27.40 ± 7.22 kg/m2) and higher levels of Chol (211 ± 67.12 mg/dl) than in sufficiency group.Secondly, participants were divided depending on BMI. Higher BMI associated with lower levels of 25OHD. Moreover, we derived that every increase in 25OHD by 1 ng/mL results in decrease of BMI by 0.26 kg/m2 (P ≤ 0.001) and results in decrease of Chol by 1.54 mg/dl (P ≤ 0.004). Conclusion: A high prevalence of 25OHD deficiency was observed in this sample of Syrian patients. There is an inverse correlation between 25OHD and BMI regardless of age and gender. Moreover, the equation, that derived between 25OHD and BMI, represents a beneficial and an inexpensive tool in clinical practice to minimize testing of 25OHD by predicting its deficiency based on BMI and supports the impact of 25OHD supplementation for reduce BMI.

8.
Adv Med ; 2020: 7014212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32149161

RESUMO

BACKGROUND: Osteoporosis and hypertension are frequent and often coexisting diseases among the elderly. Recent studies suggested that both diseases may share the same etiopathology. Moreover, the treatment of hypertension can affect the bone mineral density and worsen osteoporosis. The aim of this cross-sectional study was to assess the prevalence of low bone mass and osteoporosis in postmenopausal Syrian women and investigate their relationship with hypertension and antihypertensive drugs. METHODS: 813 postmenopausal women were involved in this cross-sectional study, aged between 40 and 96 yrs. Their menopause duration ranged between 1 and 43 yrs. Bone mineral density was measured using a dual-energy X-ray absorptiometry at the total lumbar spine (L1-L4) and left hip. T-score values were used to determine the diagnosis of osteoporosis. The existence of HTN was defined as blood pressure ≥130/85 mmHg or a history of hypertension medication. RESULTS: Using the world health organization criteria, 24% had osteoporosis and 45.2% had low bone mass. The incidence of osteoporosis and low bone mass significantly increased with age and menopause duration and decreased with BMI. Prevalence of hypertension was almost equal among the women who had or did not have osteoporosis. However, hypertensive women who used thiazides or beta blockers had higher values of total lumbar BMD compared with the women who did not. CONCLUSION: Hypertension in postmenopausal Syrian women aged over 40 was not found to be associated with osteoporosis. However, the mean total lumbar BMD of the hypertensive women who took thiazide diuretics or beta blocker was found to be increased significantly comparing to the women who did not take either.

9.
Clin Neurol Neurosurg ; 146: 52-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27150607

RESUMO

OBJECTIVE: To evaluate bone health and vitamin D adequacy in a cohort of epilepsy patients on chronic valproate (VPA) monotherapy. METHODS: Bone mineral density (BMD) using dual X-ray absorptiometry and serum concentrations of 25-hydroxyvitamin D, parathyroid hormone, calcium, phosphorus, and alkaline phosphatase were measured in 50 young adult epilepsy patients on VPA monotherapy and 50 age, sex and socioeconomically matched healthy subjects. RESULTS: Mean age of epilepsy patients was 26±7.2 (±SD) years, and females constituted 66%. Significantly lower mean lumbar spine and femoral neck BMDs (g/cm(2)) and lower femoral neck Z-score were observed in epilepsy patients in comparison with controls. Prevalence of low BMD (Z-score ≤-2.0) was 26% and 10% at lumbar spine, and 10% and 4% at femoral neck in epileptic and control groups respectively. No correlation was found between duration or dosage of VPA and BMDs. Vitamin D deficiency (≤20ng/ml) was highly prevalent (>90%) in epilepsy patients and controls. CONCLUSION: Chronic VPA therapy is associated with lower BMD measurements in young epilepsy patients. Hypovitaminosis D is highly prevalent in general population. PRACTICE IMPLICATIONS: Prophylactic and therapeutic strategies against osteoporosis should be implemented in VPA-treated patients. Routine evaluation for bone disease by measuring BMD and supplementation of calcium and vitamin D can allow effective treatment of epilepsy without bone adverse effects.


Assuntos
Anticonvulsivantes/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Ácido Valproico/efeitos adversos , Vitamina D/análogos & derivados , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Vitamina D/sangue , Adulto Jovem
10.
Arch Osteoporos ; 11: 18, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27126333

RESUMO

UNLABELLED: Vitamin D deficiency was highly prevalent in this study. More than half of the participants with vitamin D level less than 5 ng/mL had secondary hyperparathyroidism, which implicated a major bone health concern. After adjustment for potential predictors, parathyroid hormone (PTH) explained about 3 % of the variance in total hip bone mineral density (BMD). PURPOSE: Bone mineral density (BMD) is known to be influenced by serum 25-hydroxyvitamin D (25OHD) and intact parathyroid hormone (PTH) levels. The relationship between 25OHD and PTH with BMD has not been well documented in Syrian adults. We aimed to determine how differences in serum 25OHD and PTH levels impacted hip and lumbar spine BMD among apparently healthy Syrian adults. METHODS: 25OHD and PTH were measured in 156 participants aged 18-53 years from Damascus and its surroundings. Lumbar spine and hip BMD measurements were measured by dual-energy X-ray absorptiometry using Hologic Discovery Wi densitometer. Multivariate regression models were used to investigate the relationships between 25OHD, PTH, and BMD. RESULTS: All participants, except one male, had 25OHD <30 ng/mL (<75 nmol/L), and 89.1 % of them had 25OHD levels less than 20 ng/mL (50 nmol/L). Secondary hyperparathyroidism was significantly more prevalent in the lowest 25OHD quartile compared to that in the highest quartile (59 vs. 10.3 %, p < 0.0001). Mean bone mineral density at all sites in our participants was lower when compared to that of their Caucasian counterparts in Europe and North America. No significant correlation was found between 25OHD and BMD either at hip or at lumbar spine. In the multivariate analyses, after adjustment for potential predictors, PTH explained about 3 % of the variation in total hip BMD. CONCLUSIONS: Low BMD was relatively frequent at all measured sites. PTH, but not 25OHD, was a predictor for total hip BMD in a young population.


Assuntos
Densidade Óssea , Estado Nutricional , Hormônio Paratireóideo/sangue , Vitamina D/análogos & derivados , Absorciometria de Fóton , Adolescente , Adulto , Feminino , Voluntários Saudáveis , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/epidemiologia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/diagnóstico por imagem , Prevalência , Análise de Regressão , Síria/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Adulto Jovem
11.
Avicenna J Med ; 5(1): 11-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25625084

RESUMO

AIMS: To study precipitating factors, outcomes, and recurrence of diabetic ketoacidosis (DKA) at a University hospital at Damascus, the capital of Syria. PATIENTS AND METHODS: Medical records between 2006 and 2012 were reviewed. One hundred and fifteen admissions for 100 patients with DKA were included. All fulfilled the American Diabetic Association DKA diagnostic criteria. RESULTS: Of 115 admissions of DKA, there were 92 single admission and 23 recurrent admissions (eight patients). The order of precipitating factors of recurrent DKA or single admissions were the same with different percentage. The first and second factors were infection (74% and 48%) and treatment problems (17% and 24%), respectively. Complications rate was significantly higher in the intensive care unit (41.6%), compared to the ward admissions (14.2%). Overall in-hospital mortality rate was 11.3%. The severity of medical conditions that provoke DKA with aging, not the metabolic complications of hyperglycemia or ketoacidosis, were behind this high mortality rate. Patients who died were significantly (P = 0.004) older than patients who were discharged alive. CONCLUSION: Results concerning precipitating factor were similar to the results of many other studies. However, mortality rate was higher which might be explained by the severity of underlying precipitating illness.

12.
Arch Osteoporos ; 9: 176, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24715441

RESUMO

UNLABELLED: Vitamin D deficiency (25-hydroxyvitamin D (25OHD) <25 nmol/L) was common in a convenience sample of apparently healthy Syrian adults. Female gender, season, and concealing clothing were independent predictors of vitamin D deficiency. Community-based research is needed to identify vulnerable subgroups and inform public health actions. PURPOSE: Optimal vitamin D status for bone health has been inferred from the determination of serum 25OHD levels below which there is an increase in serum parathyroid hormone (PTH). Studies worldwide showed high prevalence of hypovitaminosis D even in sunny countries. There is little evidence about its prevalence among Syrian adult population. We aimed to assess the serum levels of 25OHD and factors related to vitamin D inadequacy and its relation to serum PTH and calcium among apparently healthy adults. METHODS: Serum 25OHD and PTH measurements were obtained from 372 subjects aged 18-62 years living in Damascus and its surroundings, between April 2011 and March 2013. Binary logistic regression was used to assess risk factors for hypovitaminosis D. RESULTS: The mean (standard deviation (SD)) 25OHD level was 24.7 (16.9) nmol/L [9.8 (6.7) ng/mL] and was higher in men than women (p < 0.001). Levels <25, <50, and <75 nmol/L were detected in 61, 90.1, and 99.2 % of the participants, respectively. Season influenced vitamin D status in men but not in women (p < 0.001). Female gender and wearing the veil (hijab) were independent predictors of vitamin D deficiency (25OHD <25 nmol/L). PTH was significantly higher below this threshold (p < 0.001). Serum 25OHD <25 nmol/L, sex, and age ≥ 35 years were statistically significant factors for PTH elevation. CONCLUSIONS: Vitamin D deficiency was highly prevalent in our sample. Further research is needed to identify population groups vulnerable for hypovitaminosis D and specify its predictors and inform the necessary public health measures.


Assuntos
Cálcio/sangue , Hormônio Paratireóideo/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/análogos & derivados , Adolescente , Adulto , Vestuário/efeitos adversos , Estudos Transversais , Feminino , Humanos , Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estações do Ano , Distribuição por Sexo , Síria/epidemiologia , Vitamina D/sangue , Deficiência de Vitamina D/sangue , Adulto Jovem
13.
Arthritis Rheum ; 60(8): 2220-31, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19644855

RESUMO

OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator involved in the pathogenesis of rheumatoid arthritis. This study was undertaken to identify the MIF promoter elements responsible for regulating gene expression. METHODS: Luciferase reporter gene assays were used to identify the MIF promoter sequence responsible for basal activity. Bioinformatic analysis was used to predict transcription factor binding sites, and electrophoretic mobility shift assay (EMSA) was used to demonstrate transcription factor binding. Chromatin immunoprecipitation (ChIP) was used to demonstrate transcription factor loading on the MIF promoter. RESULTS: We identified the minimal promoter sequence required for basal MIF promoter activity that was also capable of conferring glucocorticoid-dependent inhibition in a T lymphocyte model cell line. Deletion studies and EMSA revealed 2 elements in the MIF promoter that were responsible for basal promoter activity. The 5' element binds CREB/activating transcription factor 1, and the 3' element is a functional hypoxia-responsive element binding hypoxia-inducible factor 1alpha. Further studies demonstrated that the cis elements are both required for glucocorticoid-dependent inhibition. ChIP demonstrated glucocorticoid-dependent recruitment of glucocorticoid receptor alpha to the MIF promoter in lymphocytes within 1 hour of treatment and a concomitant decrease in acetylated histone H3. CONCLUSION: Our findings indicate that hypoxia and glucocorticoid signaling converge on a single element regulating MIF; this regulatory unit is a potential interacting node for microenvironment sensing of oxygen tension and glucocorticoid action in foci of inflammation.


Assuntos
Hipóxia Celular/genética , Regulação da Expressão Gênica , Glucocorticoides/metabolismo , Fatores Inibidores da Migração de Macrófagos/genética , Transdução de Sinais/genética , Sequência de Bases , Linhagem Celular , Cromatografia de Afinidade/métodos , DNA/química , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/farmacologia , Humanos , Fatores Inibidores da Migração de Macrófagos/metabolismo , Dados de Sequência Molecular , Oligonucleotídeos/química , Ligação Proteica/genética , Mucosa Respiratória/citologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Ativação Transcricional/efeitos dos fármacos , Ativação Transcricional/genética
14.
Arthritis Rheum ; 50(5): 1604-10, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15146431

RESUMO

OBJECTIVE: To establish linkage and replicate the association of macrophage migration inhibitory factor (MIF) with juvenile idiopathic arthritis (JIA). METHODS: Three hundred twenty-one Caucasian simplex families from the UK were genotyped for polymorphisms of MIF using SNaPshot ddNTP primer extension, or by a fluorescently labeled primer method, and capillary gel electrophoresis. The functional significance of the promoter polymorphisms was studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. RESULTS: MIF was linked and associated with JIA (P = 0.0016). Specifically, a 2-point promoter haplotype, CATT(7)-MIF-173*C, was found to be transmitted in excess (38 transmitted: 21 not transmitted) in the JIA patients. Conditional extended transmission disequilibrium test and pairwise extended transmission disequilibrium test predicted functional interaction between the 2 polymorphic positions. The interaction of the CATT repeat with MIF-173*G/C was found to be specific to the cell type. CONCLUSION: Replication of an association and linkage of MIF with JIA has been established. Functional interaction between the polymorphic positions on the linked haplotype has also been shown. The molecular mechanism of this interaction is currently being investigated.


Assuntos
Artrite Juvenil/genética , Fatores Inibidores da Migração de Macrófagos/genética , Artrite Juvenil/sangue , Proteína C-Reativa/metabolismo , Linhagem Celular , Genes Reporter , Ligação Genética , Haplótipos , Humanos , Fatores Inibidores da Migração de Macrófagos/sangue , Polimorfismo Genético , Regiões Promotoras Genéticas , Mucosa Respiratória/citologia , Linfócitos T/citologia , Transfecção
15.
Arthritis Rheum ; 46(9): 2402-9, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12355488

RESUMO

OBJECTIVE: To determine if polymorphisms of the macrophage migration inhibitory factor (MIF) gene are associated with juvenile idiopathic arthritis (JIA). METHODS: Denaturing high-performance liquid chromatography was used to screen the MIF gene in 32 UK Caucasian controls and 88 UK Caucasian JIA patients. Ninety-two healthy UK Caucasian controls were then genotyped for each of the polymorphic positions identified. A panel of 526 UK Caucasian JIA patients and 259 UK Caucasian controls were subsequently genotyped for a single-nucleotide polymorphism (SNP) identified in the 5'-flanking region of the gene, using SNaPshot ddNTP primer extension and capillary electrophoresis. The functional significance of this polymorphism was also studied using luciferase-based reporter gene assays in human T lymphoblast and epithelial cell lines. RESULTS: A tetranucleotide repeat CATT((5-7)) beginning at nucleotide position -794 and 3 SNPs at positions -173 (G to C), +254 (T to C), and +656 (C to G) of the MIF gene were identified. No JIA-specific mutations were found. Allele and genotype frequencies differed significantly between the controls and the JIA patients for the MIF-173 polymorphism. Individuals possessing a MIF-173*C allele had an increased risk of JIA (34.8% versus 21.6%) (odds ratio 1.9, 95% confidence interval 1.4-2.7; P = 0.0002). Furthermore, the MIF-173* G and C variants resulted in altered expression of MIF in a cell type-specific manner. Serum levels of MIF were also significantly higher in individuals who carried a MIF-173*C allele (P = 0.04). CONCLUSION: The -173-MIF*C allele confers increased risk of susceptibility to JIA. Our data suggest a cell type-specific regulation of MIF, which may be central to understanding its role in inflammation.


Assuntos
Artrite Juvenil/genética , Análise Mutacional de DNA , Testes Genéticos , Fatores Inibidores da Migração de Macrófagos/genética , Polimorfismo Genético , Alelos , Artrite Juvenil/sangue , Linhagem Celular , Frequência do Gene , Genes Reporter , Predisposição Genética para Doença , Genótipo , Humanos , Fatores Inibidores da Migração de Macrófagos/sangue , Repetições de Microssatélites , Valores de Referência , Transfecção
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