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1.
J Public Health Afr ; 14(1): 2242, 2023 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-36798849

RESUMEN

Background: Seroprevalence studies, to estimate the proportion of people that has been infected by SARS-CoV-2 are importance in African countries, where incidence is among the lowest in the world. Objective: This study aimed at evaluating the exposure to SARS-CoV-2 within a university setting of Cameroon. Methods: A cross-sectional study performed in December 2020 - December 2021, among students and staffs of the Evangelical University of Cameroon. COVID-19 antigen rapid detection test (RDT) was performed using Standard Q Biosensor, and one year after SARS-CoV-2 antibody-test was performed within the same population using RDT and chemiluminescence immunoassay (CLIA). Results: 106 participants were enrolled (80% students), female sex was the most represented. Positivity to SARS-CoV-2 was 0.0% based on antigen RDTs. The seroprevalence of SARSCoV- 2 antibodies was estimated at 73.6% (95% CI. 64.5-81.0) for IgG and 1.9% (95% CI. 0.2-6.8) for IgM/IgG with RDTs, and 91.9% (95% CI. 84.7-96.4) for anti-nucleocapsid with CLIA. 95.3% (101) reported having developed at least one of the known COVID-19 symptoms (cough and headache being the most common). 90.3% (28) of people who experienced at least one of these symptoms developed IgG antibodies. 40.6% (43) of participants took natural herbs, whereas 55.7% (59) took conventional drugs. The most used herb was Zingiber officinale, while the most used drugs were antibiotics. Conclusion: In this Cameroonian University community, SARS-CoV-2 seroprevalence is high, with a greater detection using advanced serological assays. This indicates a wide viral exposure, and the need to adequate control measures especially for those experiencing any related COVID-19 symptoms.

2.
Sci Rep ; 11(1): 9007, 2021 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-33903708

RESUMEN

MicroRNAs constitute a class of noncoding small RNAs involved in the posttranscriptional regulation of many biological pathways. In recent years, microRNAs have also been associated with regulation across kingdoms, demonstrating that exogenous miRNAs can function in mammals in a fashion similar to mammalian miRNAs. The growing interest in microRNAs and the increasing amount of literature and molecular and biomedical data available make it difficult to identify records of interest and keep up to date with novel findings. For these reasons, we developed the microRNA Analysis Portal (MAP). MAP selects relevant miRNA-focused articles from PubMed, links biomedical and molecular data and applies bioinformatics modules. At the time of this writing, MAP represents the richest, most complete and integrated database focused on microRNAs. MAP also integrates an updated version of MirCompare (2.0), a computational platform used for selecting plant microRNAs on the basis of their ability to regulate mammalian genes. Both MAP and MirCompare functionalities were used to predict that microRNAs from Moringa oleifera have putative roles across kingdoms by regulating human genes coding for proteins of the immune system. Starting from a selection of 94 human microRNAs, MirCompare selected 6 Moringa oleifera functional homologs. The subsequent prediction of human targets and areas of functional enrichment highlighted the central involvement of these genes in regulating immune system processes, particularly the host-virus interaction processes in hepatitis B, cytomegalovirus, papillomavirus and coronavirus. This case of use showed how MAP can help to perform complex queries without any computational background. MAP is available at http://stablab.uniroma2.it/MAP .


Asunto(s)
MicroARNs/genética , Análisis de Secuencia de ARN/métodos , Genes de Plantas , Moringa oleifera/genética , Análisis de Componente Principal
3.
Sci Rep ; 9(1): 18573, 2019 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-31797912

RESUMEN

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

4.
Sci Rep ; 9(1): 15145, 2019 10 22.
Artículo en Inglés | MEDLINE | ID: mdl-31641153

RESUMEN

MicroRNAs, a class of small, non-coding RNAs, play important roles in plant growth, development and stress response by negatively regulating gene expression. Moringa oleifera Lam. plant has many medical and nutritional uses; however, little attention has been dedicated to its potential for the bio production of active compounds. In this study, 431 conserved and 392 novel microRNA families were identified and 9 novel small RNA libraries constructed from leaf, and cold stress treated callus, using high-throughput sequencing technology. Based on the M. oleifera genome, the microRNA repertoire of the seed was re-evaluated. qRT-PCR analysis confirmed the expression pattern of 11 conserved microRNAs in all groups. MicroRNA159 was found to be the most abundant conserved microRNA in leaf and callus, while microRNA393 was most abundantly expressed in the seed. The majority of predicted microRNA target genes were transcriptional factors involved in plant reproduction, growth/development and abiotic/biotic stress response. In conclusion, this is the first comprehensive analysis of microRNAs in M. oleifera leaf and callus which represents an important addition to the existing M. oleifera seed microRNA database and allows for possible exploitation of plant microRNAs induced with abiotic stress, as a tool for bio-enrichment with pharmacologically important phytochemicals.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Genes de Plantas , MicroARNs/genética , Moringa oleifera/genética , Hojas de la Planta/genética , Frío , Ontología de Genes , MicroARNs/metabolismo , ARN de Planta/genética , ARN de Planta/metabolismo , Reproducibilidad de los Resultados
5.
J Nat Prod ; 82(9): 2379-2386, 2019 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-31430152

RESUMEN

Moringa oleifeira has recently been subjected to numerous scientific studies pursuing its biological properties. However, biotechnological approaches promoting the synthesis of pharmacological compounds in this species are still scarce, despite the fact that moringa metabolites have shown significant nutraceutical effects. For this reason, in vitro cultures of moringa callus, obtained from leaf explantation, were subjected to various abiotic stresses such as temperature, salicylic acid, and NaCl, to identify the best growth conditions for the production of high levels of antioxidant molecules. Temperature stresses (exposure to 4 and 45 °C) led to no significant variation in moringa callus, in terms of antiradical metabolites, whereas salicylic acid (200 µM) and NaCl (50-100 µM) affected an increase of total phenolic compounds, after 15 and 30 days of treatment. Overall, the treatment with 100 µM NaCl for 30 days showed the highest free radical scavenging activity, comparable to that measured in moringa leaf. In addition, high doses of NaCl (200 µM) inhibited callus growth and reduced the amount and bioactivity of the secondary metabolites of callus. This study provides useful information to standardize growth conditions for the production of secondary metabolites in moringa in vitro cultures, a biotechnological system that could be employed for a rapid, controlled, and guaranteed production of antioxidant molecules for pharmaceutical purposes.


Asunto(s)
Antioxidantes/metabolismo , Moringa oleifera/metabolismo , Estrés Fisiológico , Extractos Vegetales/metabolismo , Hojas de la Planta/metabolismo , Cloruro de Sodio/farmacología
6.
Sci Rep ; 9(1): 10480, 2019 07 19.
Artículo en Inglés | MEDLINE | ID: mdl-31324861

RESUMEN

High-throughput technologies have produced a large amount of experimental and biomedical data creating an urgent need for comprehensive and automated mining approaches. To meet this need, we developed SMAC (SMart Automatic Classification method): a tool to extract, prioritise, integrate and analyse biomedical and molecular data according to user-defined terms. The robust ranking step performed on Medical Subject Headings (MeSH) ensures that papers are prioritised based on specific user requirements. SMAC then retrieves any related molecular data from the Gene Expression Omnibus and performs a wide range of bioinformatics analyses to extract biological insights. These features make SMAC a robust tool to explore the literature around any biomedical topic. SMAC can easily be customised/expanded and is distributed as a Docker container ( https://hub.docker.com/r/hfx320/smac ) ready-to-use on Windows, Mac and Linux OS. SMAC's functionalities have already been adapted and integrated into the Breast Cancer Now Tissue Bank bioinformatics platform and the Pancreatic Expression Database.


Asunto(s)
Minería de Datos , Expresión Génica , Almacenamiento y Recuperación de la Información , Publicaciones Periódicas como Asunto , Biología Computacional/métodos , Sistemas de Computación , Minería de Datos/métodos , Humanos , Almacenamiento y Recuperación de la Información/métodos , Sistemas de Información , Medical Subject Headings , Metadatos , Programas Informáticos
7.
Sci Rep ; 8(1): 12413, 2018 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-30120339

RESUMEN

Functional foods include compounds with nutritional and health properties. The human diet could play a stronger role in cancer prevention. Only a few studies have described the presence of plant small RNA, in humans who were fed with plant foods, which demonstrated the ability of these molecules to modulate consumer's genes and evidenced the existence of a plant-animal regulation. Through in silico prediction, Olea europaea small RNAs (sRs), which had been previously reported as miRNAs, were identified, each with functional homology to hsa-miR34a. According to this initial funding, we investigated the ability of oeu-sRs to regulate tumorigenesis in human cells. The transfection of these synthetic oeu-sRs reduced the protein expression of hsa-miR34a mRNA targets, increased apoptosis and decreased proliferation in different tumor cells; by contrast, no effect was observed in PBMCs from healthy donors. The introduction of oeu-small RNA in hsa-miR34a-deficient tumor cells restores its function, whereas cells with normal expression of endogenous hsa-miR34a remained unaffected. The natural oeu-small RNAs that were extracted from O. europaea drupes induce the same effects as synthetic sRs. Careful research on the small RNA sequences executed for mapping and annotation in the genome of O. europaea var. Sylvestris and var. Farga led to the hypothesis that RNA fragments with functional homology to human miRNAs could be generated from the degradation of regions of RNA transcripts. These results indicate the possibility of developing novel natural non-toxic drugs that contain active plant-derived tumor-suppressing small RNA with functional homology to hsa-miRNAs and that can support antineoplastic strategies.


Asunto(s)
Evolución Molecular , MicroARNs/genética , Neoplasias/genética , Olea/genética , Interferencia de ARN , ARN de Planta/genética , Apoptosis/genética , Biomarcadores , Línea Celular Tumoral , Supervivencia Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/química , ARN de Planta/química , Homología de Secuencia de Ácido Nucleico , Transfección
8.
J Public Health Afr ; 9(3): 841, 2018 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-30854178

RESUMEN

Diet and nutrition are important factors in the promotion and maintenance of good health throughout the entire life course. A plant-based diet may be able to prevent and treat chronic diseases such as diabetes, heart disease and hypertension, obesity, chronic inflammation and cancer. Phytonutrient rich foods are found in traditional African diet which is mostly vegetarian, and most of these food plants are often used for medicinal purposes. This review focuses on a peculiar plant Moringa oleifera, called the "Miracle Tree", considered to be one of nature's healthiest and most nutritious foods. Countless studies describe the benefits of Moringa leaves, pods, seeds and flowers. Its well-documented role in prevention and treatment of chronic diseases is hypothesized here as a result of possible of cross-kingdom regulation by exogenous vegetal microRNAs and synergistic action of plant bioactive components on endogenous human microRNA regulation. The potential health impact of phytocomplexes from African dietary plants within the context of cross-kingdom and endogenous microRNA regulation on health improvement and the overall economic well-being of the continent is estimated to be enormous.

9.
J. Public Health Africa (Online) ; 9(3): 191-199, 2018. ilus
Artículo en Inglés | AIM (África) | ID: biblio-1263278

RESUMEN

Diet and nutrition are important factors in the promotion and maintenance of good health throughout the entire life course. A plant-based diet may be able to prevent and treat chronic diseases such as diabetes, heart disease and hypertension, obesity, chronic inflammation and cancer. Phytonutrient rich foods are found in traditional African diet which is mostly vegetarian, and most of these food plants are often used for medicinal purposes. This review focuses on a peculiar plant Moringa oleifera, called the "Miracle Tree", considered to be one of nature's healthiest and most nutritious foods. Countless studies describe the benefits of Moringa leaves, pods, seeds and flowers. Its well-documented role in prevention and treatment of chronic diseases is hypothesized here as a result of possible of cross-kingdom regulation by exogenous vegetal microRNAs and synergistic action of plant bioactive components on endogenous human microRNA regulation. The potential health impact of phytocomplexes from African dietary plants within the context of cross-kingdom and endogenous microRNA regulation on health improvement and the overall economic well-being of the continent is estimated to be enormous


Asunto(s)
África , Enfermedad Crónica , Suplementos Dietéticos , Moringa oleifera/uso terapéutico , Plantas Medicinales
10.
J Comput Biol ; 23(12): 976-989, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-27428722

RESUMEN

MicroRNAs (miRNAs) are a class of small noncoding RNAs that act as efficient post-transcriptional regulators of gene expression. In 2012, the first cross-kingdom miRNA-based interaction had been evidenced, demonstrating that exogenous miRNAs act in a manner of mammalian functional miRNAs. Starting from this evidence, we defined the concept of cross-kingdom functional homology between plant and mammalian miRNAs as a needful requirement for vegetal miRNA to explicit a regulation mechanism into the host mammalian cell, comparable to the endogenous one. Then, we proposed a new dedicated algorithm to compare plant and mammalian miRNAs, searching for functional sequence homologies between them, and we developed a web software called MirCompare. We also predicted human genes regulated by the selected plant miRNAs, and we determined the role of exogenous miRNAs in the perturbation of intracellular interaction networks. Finally, as already performed by Pirrò and coworkers, the ability of MirCompare to select plant miRNAs with functional homologies with mammalian ones has been experimentally confirmed by evaluating the ability of mol-miR168a to downregulate the protein expression of SIRT1, when its mimic is transfected into human hepatoma cell line G2 (HEPG2) cells. This tool is implemented into a user-friendly web interface, and the access is free to public through the website http://160.80.35.140/MirCompare.


Asunto(s)
Algoritmos , Biología Computacional/métodos , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , MicroARNs/genética , Moringa oleifera/genética , Células Hep G2 , Humanos , Mapeo de Interacción de Proteínas , ARN Mensajero/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Programas Informáticos
11.
PLoS One ; 11(3): e0149495, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26930203

RESUMEN

Moringa oleifera is a widespread plant with substantial nutritional and medicinal value. We postulated that microRNAs (miRNAs), which are endogenous, noncoding small RNAs regulating gene expression at the post-transcriptional level, might contribute to the medicinal properties of plants of this species after ingestion into human body, regulating human gene expression. However, the knowledge is scarce about miRNA in Moringa. Furthermore, in order to test the hypothesis on the pharmacological potential properties of miRNA, we conducted a high-throughput sequencing analysis using the Illumina platform. A total of 31,290,964 raw reads were produced from a library of small RNA isolated from M. oleifera seeds. We identified 94 conserved and two novel miRNAs that were validated by qRT-PCR assays. Results from qRT-PCR trials conducted on the expression of 20 Moringa miRNA showed that are conserved across multiple plant species as determined by their detection in tissue of other common crop plants. In silico analyses predicted target genes for the conserved miRNA that in turn allowed to relate the miRNAs to the regulation of physiological processes. Some of the predicted plant miRNAs have functional homology to their mammalian counterparts and regulated human genes when they were transfected into cell lines. To our knowledge, this is the first report of discovering M. oleifera miRNAs based on high-throughput sequencing and bioinformatics analysis and we provided new insight into a potential cross-species control of human gene expression. The widespread cultivation and consumption of M. oleifera, for nutritional and medicinal purposes, brings humans into close contact with products and extracts of this plant species. The potential for miRNA transfer should be evaluated as one possible mechanism of action to account for beneficial properties of this valuable species.


Asunto(s)
MicroARNs/genética , Moringa oleifera/genética , Plantas Medicinales/genética , ARN de Planta/genética , Secuencia de Bases , Secuencia Conservada , Regulación de la Expresión Génica de las Plantas , Genómica , Células Hep G2 , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , MicroARNs/química , MicroARNs/farmacología , Moringa oleifera/química , Plantas Medicinales/química , ARN de Planta/química , ARN de Planta/farmacología , Análisis de Secuencia de ARN/métodos , Transfección
12.
Hum Immunol ; 74(1): 52-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23079236

RESUMEN

The frequencies of HLA-A, HLA-B and HLA-DRB1 alleles in 118 unrelated Libyans from Benghazi (Cyrenaica) were analysed using high resolution typing and compared with other populations. Their relatedness has been tested by correspondence analyses and principal component analysis. The most frequent HLA-A alleles were A(∗)02:01:01:01 (15.7%), A(∗)01:01:01:01 (11.4%) and A(∗)03:01:01:01 (9.3%). For the HLA-B locus, the commonest allele was HLA-B(∗)50:01:01 (14.4%) followed by B(∗)51:01:01 (9.8%) and B(∗)08:01:01 (6.4%). For the HLA-DRB1 locus, the commonest was HLA-DRB1(∗)07:01:01:01 (16.9%) followed by DRB1(∗)03:01:01:01 (13.6%) and DRB1(∗)13:02:01 (9.3%). The most frequent two-locus haplotypes were HLA-A(∗)02:01:01:01-B(∗)07:02:01 (3.0%) and HLA-B(∗)50:01:01-DRB1(∗)07:01:01:01 (9.6%), and three-locus haplotypes were HLA-A(∗)02:01:01:01-B(∗)50:01:01-DRB1(∗)07:01:01:01 (4.2%) and HLA-A(∗)11:01:01-B(∗)52:01:01:01-DRB1(∗)15:02:01 (2.5%). This study is the first on the HLA status of a Libyan population. The results, when compared to similar HLA data obtained previously from African and Mediterranean populations, indicate genetic influences from several ethnic groups. Moreover, the differences in the HLA allele frequencies between the Libyan population and others reveals that significant admixture has occurred between the original Berber inhabitants and neighbouring and more distant populations, even though a strong genetic Berber substratum remains. These data will be of value to future anthropological and disease association studies involving the Libyan population.


Asunto(s)
Etnicidad/genética , Frecuencia de los Genes , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadenas HLA-DRB1/genética , Polimorfismo Genético , Alelos , Niño , Preescolar , Femenino , Genética de Población , Haplotipos , Humanos , Lactante , Libia , Masculino , Análisis de Componente Principal
13.
J Antimicrob Chemother ; 67(12): 2932-8, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22915460

RESUMEN

OBJECTIVES: To evaluate the correlations of the combination of undetectable HIV-DNA (<10 copies/10(6) peripheral blood mononuclear cells) and HIV-RNA (<1 copy/mL of plasma) levels and a CD4 cell count of >500 cells/mm(3) (defined as the treatment goal) in a group of 420 antiretroviral treatment (ART) responder patients. METHODS: A cross-sectional, open-label, multicentre trial was conducted in a cohort of 420 HIV-infected ART-treated subjects with viral loads persistently <50 copies/mL for a median observation time of 28.8 months. HIV-DNA and residual viraemia values and demographic, virological and immunological data were collected for each subject. RESULTS: Undetectable HIV-DNA was found in 16.6% (70/420) of patients and was significantly correlated with undetectable (<1 copy/mL) plasma viraemia (P = 0.0001). Higher CD4 cell count nadir (P < 0.001), a lower HIV-RNA viraemia at the start of treatment (P = 0.0016) and nevirapine use (P < 0.001) were correlated with an undetectable value of HIV-RNA. Twenty-six out of 420 patients (6.2%) reached the treatment goal. In multivariate analysis, higher nadir CD4 cell count (OR 3.86, 95% CI 1.47-10.16, P = 0.006), the duration of therapy (OR 1.07, 95% CI 1.02-1.12, P = 0.004) and the use of nevirapine (OR 2.59, 95% CI 1.07-6.28, P = 0.034) were independently related to this condition. CONCLUSIONS: Only 6.2% of ART-responder patients presented the combination of three laboratory markers that identified them as full responders. These results indicate the high variability of the ART-responding population and lead us to suggest caution in the selection of patients for possible simplification regimens.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Infecciones por VIH/tratamiento farmacológico , Nevirapina/administración & dosificación , Carga Viral , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4 , Estudios Transversales , ADN Viral/sangre , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , ARN Viral/sangre , Resultado del Tratamiento , Estados Unidos
14.
Dis Markers ; 29(5): 259-64, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21206011

RESUMEN

Several studies suggest that the peroxisome proliferator-activated receptor gamma (PPARγ) is involved in atherogenesis. The Pro12Ala polymorphism in the gene encoding PPARγ (PPARγ2 gene) influences the risk for type 2 diabetes. Two population-based studies have shown that the Ala allele is associated with reduced carotid intimal-medial thickness (IMT). However, studies focusing on acute clinical events have yielded conflicting results. Our aim was to evaluate the role of the Pro12Ala PPARγ2 polymorphism on the risk of coronary artery disease (CAD) in an Italian population with a case-controlled genetic association study in which 478 CAD patients and 218 controls were genotyped for the Pro12Ala polymorphism. CAD was diagnosed by angiography. We found that homozygotes for the Ala12 allele had a significantly reduced risk of CAD after adjusting for diabetes, sex, age, body mass index (BMI), smoking, lipids and hypertension (OR =0.007; 95% C.I. = 0.00-0.32 p< 0.011). In this case-control study, homozygosity for the Ala allele at codon 12 of the PPARγ2 gene resulted in reduced risk of CAD. This is consistent with reports from previous studies focusing on atherosclerosis and myocardial infarction.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , PPAR gamma/genética , Polimorfismo de Nucleótido Simple , Enfermedad de la Arteria Coronaria/epidemiología , Femenino , Estudios de Asociación Genética , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Método Simple Ciego
15.
Hum Immunol ; 69(4-5): 291-300, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18486765

RESUMEN

Patients with high-risk human leukocyte antigen (HLA)-DR-DQ genotypes for type 1 diabetes (T1D) were compared with HLA-matched controls to evaluate T1D risk for other HLA loci, including HLA-A, -B, -Cw, and DPB1. Patients (n = 133) with high-risk genotypes (DR3/DR3, DR3/DR4, DR4/DR4) were selected from the Lazio (Rome) region of Italy. Screening of more than 9000 patients from the Lazio region and northern Italy yielded 162 controls with high-T1D-risk haplotypes. Although the overall distributions did not differ significantly, allele frequency differences were discovered between the controls from Lazio and controls from northern Italy for some alleles previously determined to affect T1D risk, such as A*3002, DPB1*0301, and DPB1*0402. Therefore, Lazio patient data were compared both with the Lazio subset of controls (n = 53) and with the entire group of controls for association analyses. Significant allele frequency differences between patients and DR-DQ-matched controls existed for specific alleles at all loci. Data for the DR3/DR3 subset of patients and controls demonstrated an increase of Cw*0702 in patients. Compared with controls, reduced patient frequencies were seen for several alleles, including A*0101, B*0801, and Cw*0701, all on the highly conserved, extended DR3 haplotype known as 8.1 in DR3/DR3, but not DR3/DR4, subgroup. DPB1*0101, often reported on 8.1 haplotypes, was also less frequent in DR3/DR3 patients than controls. Analysis of family-based data from the HBDI repository was consistent with the observed results from the Italian patients, indicating the presence of a T1D-protective locus at or near A*0101 and a second T1D-protective locus at or near DPB1*0101. These data indicate that T1D risk conferred by the 8.1 haplotype is genotype dependent.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Antígenos HLA-A/genética , Antígenos HLA-DP/genética , Antígeno HLA-DR3/genética , Antígeno HLA-DR4/genética , Haplotipos , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/epidemiología , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Antígeno HLA-A1 , Antígenos HLA-B/genética , Antígeno HLA-B8 , Cadenas beta de HLA-DP , Heterocigoto , Homocigoto , Humanos , Recién Nacido , Italia/epidemiología
16.
Eur J Hum Genet ; 14(1): 94-100, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16251889

RESUMEN

Adrenergic receptors regulate lipid mobilization, energy expenditure and glycogen breakdown. The beta(2) adrenergic receptor (beta(2)-AR) gene may constitute a potential candidate gene to explain part of the genetic predisposition to human obesity and correlated traits. With regard to the association between beta(2)-AR gene polymorphisms and obesity-related metabolic disorders, published reports give conflicting results. We investigated the role of three polymorphisms, and related haplotypes of the beta(2)-AR in the obesity and related traits in a cohort of overweight/obese subjects. We characterized one single nucleotide polymorphism (SNP) in the promoter region (5'LC-Cys19Arg) and two in the coding region (Gly16Arg and Gln27Glu) of the beta(2)-AR in 642 consecutively recruited overweight/obese subjects in whom extensive clinical and biochemical analysis was performed. The effect of the polymorphisms on quantitative variables was investigated using multiple linear regression analysis. 5'LC-Cys19 homozygous showed higher triglyceride and LDL-cholesterol levels compared to 5'LC-Arg19 homozygous (P=0.03 and P=0.01, respectively). Similar increase in triglyceride and LDL-cholesterol levels was observed for Arg/Arg genotype compared to Gly/Gly genotype of Gly16Arg polymorphism (P=0.02 and P=0.01, respectively) and for Gln/Gln genotype compared to Glu/Glu genotype of the Gln27Glu polymorphism (P=0.01 and P=0.03, respectively). The 5'LC-Cys(19)Arg(16)Gln(27) haplotype determined a significant increase in triglyceride and LDL-cholesterol levels compared to 5'LC-Arg(19)Gly(16)Glu(27) haplotype (P=0.05 and P=0.02, respectively). Our findings provide additional weight to previous observations on the influence of these three genetic variants on lipid phenotypes; particularly on the increase of triglycerides and LDL-cholesterol levels in overweight/obese subjects carrying the 5'LC-Cys(19)Arg(16)Gln(27) haplotype.


Asunto(s)
LDL-Colesterol/sangre , Haplotipos/genética , Sobrepeso/genética , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Triglicéridos/sangre , Estudios de Cohortes , Femenino , Frecuencia de los Genes , Humanos , Italia , Desequilibrio de Ligamiento , Masculino , Obesidad/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas
17.
Thyroid ; 15(3): 232-8, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15785242

RESUMEN

Graves' disease (GD) is an autoimmune and polygenic disorder. Several studies have shown that human leukocyte antigen (HLA) class II and the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) gene are involved in the genetic susceptibility. We performed a case control study on 150 patients with GD and 301 controls, matched for age and gender, to verify the association of three polymorphisms located in CTLA-4 region (A49G, [AT](n)-3'UTR, and CT60) and of HLA-DRB1 and DQB1 loci with the disease in an Italian population. The prevalence of patients with GD carrying the G allele of CT60 was significantly higher compared to control subjects (p = 0.02, odds ratio [OR] = 1.82). The allelic frequency of the G allele of CT60 was also significantly higher in patients with GD (p = 0.02). The G allele frequency of A49G in patients was significantly higher compared to control subjects (p = 0.04). The 280 allele phenotype frequency of (AT)(n)-3'UTR was also significantly higher in patients (p = 0.04). The G allele of A49G, the G allele of CT60, and the 280 allele of (AT)(n)-3'UTR microsatellite were significantly increased in patients with GD with thyroid-associated ophthalmopathy (TAO) compared to controls (p = 0.04, p = 0.03, and p = 0.02, respectively), however, we did not find any significant difference between TAO and non-TAO patients. We also found the HLA-DRB1*03 allele to be associated with GD; interestingly, the association of the CTLA-4 markers was independent from the HLA DRB1*03 status. These results highlight the role of the CTLA-4 locus, in addition to HLA, in the susceptibility to GD. Inside the CTLA-4 region, CT60 appears to be the most associated polymorphism to GD, however, further studies are needed to identify the etiologic variant.


Asunto(s)
Antígenos de Diferenciación/genética , Enfermedad de Graves/genética , Enfermedad de Graves/inmunología , Polimorfismo de Nucleótido Simple , Regiones no Traducidas 5' , Antígenos CD , Antígeno CTLA-4 , Cartilla de ADN , Frecuencia de los Genes , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad , Humanos , Italia , Repeticiones de Microsatélite , Fenotipo , Reacción en Cadena de la Polimerasa , Valores de Referencia , Población Blanca
18.
Hum Immunol ; 65(4): 366-72, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15120192

RESUMEN

As part of a longitudinal study aimed at defining the natural history of prediabetic autoimmunity and predicting the risk of future cases of type 1 diabetes, 3607 newborns from three regions of continental Italy (Lombardia, Liguria, and Lazio) were subjected to genetic testing to determine human leukocyte antigen-DRB1 (HLA-DRB1) and -DQB1 allele and phenotype frequencies. Polymerase chain reaction and immobilized sequence-specific oligonucleotide probe assays were used to identify ten DRB1 allele lineages and three DQB1 alleles. No major inter-regional differences emerged in the allelic distribution indicating homogeneous distribution of the HLA DRB1-DQB1 alleles among the three regions analyzed. Comparison of our data with those published for other Caucasian populations reveals that these three regions are characterized by a very low frequency of DRB1*04 (8%) and a high frequency of DRB1*11 (25%). The phenotype frequencies of HLA-DQB1*0302 and DQB1*0602 observed are also lower than those reported for other populations. Furthermore, the DRB1*04-DQB1*0302 haplotype was relatively infrequent in our population (5.3% of the newborns tested). These findings furnish a genetic "portrait" of the populations of the analyzed regions that will be useful not only for investigation of the genetic risk of type 1 diabetes mellitus in Italy but also for studies of other autoimmune diseases related to HLA genotypes.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Frecuencia de los Genes , Antígenos HLA-DR/genética , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Cadenas beta de HLA-DQ , Cadenas HLA-DRB1 , Prueba de Histocompatibilidad , Humanos , Recién Nacido , Italia/epidemiología
19.
Diabetes ; 51(5): 1649-50, 2002 May.
Artículo en Inglés | MEDLINE | ID: mdl-11978670

RESUMEN

A polymorphism in the interleukin 12B gene was recently reported to be strongly associated with type 1 diabetes in 422 Australian and British families. We analyzed the same polymorphism in 470 Italian type 1 diabetic patients and 544 matched control subjects and found no evidence of association with the disease.


Asunto(s)
Diabetes Mellitus Tipo 1/genética , Interleucina-12/genética , Polimorfismo Genético , Adolescente , Adulto , Estudios de Casos y Controles , Niño , Diabetes Mellitus Tipo 1/epidemiología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Italia/epidemiología , Masculino , Factores de Riesgo
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