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1.
Anticancer Res ; 40(7): 3619-3631, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620601

RESUMO

MMP-2 and MMP-9 genes have been suggested to play a role in breast cancer. Their functions have been associated with invasion and metastasis of breast cancer; however, their involvement in the development of the disease is not well-established. Herein, we reviewed the literature investigating the association between circulating levels and polymorphisms of MMP-2 and MMP-9 and breast cancer risk. Various studies report conflicting results regarding the relationship of polymorphisms in MMP-2 and MMP-9 and breast cancer risk. Nevertheless, it appears that the T allele in rs243865 and rs2285053 in MMP-2 are associated with reduced risk of breast cancer. In addition, high levels of latent form and low levels of active form of MMP-2 were observed in breast cancer patients compared to controls. For MMP-9, high latent levels and low total levels were found in breast cancer patients compared to controls. Additional studies are needed to comprehend the role of these genes in breast carcinogenesis.


Assuntos
Neoplasias da Mama/etiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético/fisiologia , Alelos , Feminino , Humanos , Risco
2.
Gerokomos (Madr., Ed. impr.) ; 31(2): 113-118, jun. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-193893

RESUMO

INTRODUCCIÓN: La presencia del pie diabético es una complicación frecuente en la persona que vive con diabetes. En su etiopatogenia confluyen factores conductuales, ambientales y el control de la enfermedad; no obstante, se reconoce la influencia de factores genéticos en su desarrollo y evolución. OBJETIVO: Sistematizar la asociación de los polimorfismos genéticos como riesgo para el desarrollo de pie diabético a través de la producción científica indexada. METODOLOGÍA: Revisión bibliográfica de los años 2010 a 2018; se realizó mediante la búsqueda sistemática en las bases de datos PubMed, Scopus, CONRICYT y WOS. Los descriptores fueron tres: "polymorphism" AND "diabetic foot" OR "foot ulcer diabetic". Se incluyeron artículos a texto completo en inglés con metodología de casos y controles, y que midieran estadísticamente factores de riesgo mediante la odds ratio y los riesgos relativos. Se utilizó la plataforma FLC 2.0 para evaluar la calidad del estudio. RESULTADOS: 13 artículos cumplieron con los criterios de inclusión; se identificaron 9 polimorfismos como factores para la aparición de pie diabético: HIF-1α, MCP-1-2518A/G, TLR9-1237 T/C, MAPK14 rs80028505, LOX G473A, gen FokI del receptor VDR, MMPs-1562C>T, TCF7L2, HIF-1α p582s y 4 como factores protectores: VEGF rs699947, VEGF-634G/C, eNOS Glu298Asp y VEGF 2578 C/A. CONCLUSIÓN: La susceptibilidad, gravedad y aparición del pie diabético está asociado con factores genéticos implicados en distintos mecanismos fisiopatológicos


INTRODUCTION: Diabetic foot is a frequent complication in patients with diabetes. The risk factors associated with its development and evolution are related to the behavioral, environmental and disease control characteristics, however, the influence of genetic factors in the development of this complication has been recognized. OBJECTIVE: To analyze the available evidence on the association of genetic polymorphisms in the risk of presenting diabetic foot. METHODOLOGY: Articles were reviewed in English, not older than 10 years, with a methodology of cases and controls that statistically measure risk factors through odds ratio and relative risk. Therefore the search was performed in databases such as PubMed, Scopus, CONRICYT and WOS with maximum date until January 31, 2018. Controlled descriptors "polymorphism" AND "diabetic foot" OR "foot ulcer diabetic" were applied. The FLC 2.0 platform was used to evaluate the quality of the study. RESULTS: Thirteen articles were selected, there being 9 polymorphisms with risk factors such as HIF-1α, MCP-1-2518A/G, TLR9-1237 T/C, MAPK14 rs80028505, LOX G473A, FokI gene of the VDR receptor, MMPs-1562C>T, TCF7L2, HIF-1α p582s and 4 protective factors such as VEGF rs699947, VEGF-634G/C, eNOS Glu298Asp and VEGF 2578 C/A. CONCLUSION: The susceptibility, severity and appearance of diabetic foot they are associated with genetic factors that are involved in different physiopathological mechanisms


Assuntos
Humanos , Polimorfismo Genético/fisiologia , Pé Diabético/enfermagem , Pé Diabético/complicações , Pé Diabético/etiologia , Pé Diabético/genética , Fatores de Risco , Razão de Chances
3.
Proc Natl Acad Sci U S A ; 117(21): 11636-11647, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32404419

RESUMO

Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.


Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Células Matadoras Naturais/fisiologia , Polimorfismo Genético/genética , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/fisiologia , Humanos , Ativação Linfocitária/genética , Modelos Moleculares , Polimorfismo Genético/fisiologia , Receptores KIR/genética
4.
Rev. esp. nutr. comunitaria ; 26(1): 0-0, ene.-mar. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-193825

RESUMO

FUNDAMENTOS: El estado nutricional puede verse afectado por la conducta alimentaria y los ritmos circadianos. Estos se encuentran regulados por el gen CLOCK, cuyos alelos T del SNP rs3749474T/C y A del SNP rs4864548A/G, han sido asociados con la obesidad en adultos. MÉTODOS: Se evaluó a 65 sujetos usando la técnica PCR en tiempo real para determinar si era portadores del alelo T del SNP rs3749474T/C o del A del SNP rs4864548A/G. Se realizaron mediciones antropométricas, y se aplicó los cuestionarios TFEQ y el Horne-Östberg. RESULTADOS: De los 65 sujetos estudiados, 8 eran portadores del alelo T del SNP rs3749474T/C y 7 del A del SNP rs4864548A/G. Los portadores del alelo A presentaron mayores valores promedio de IMC (26,58), circunferencia de cintura (89,57cm) y porcentaje de grasa (31,56%) no existiendo diferencias estadísticamente significativas entre ellos. No se encontraron diferencias estadísticamente significativas en cuanto a la conducta alimentaria. El 66,67% del total de los sujetos presentó un cronotipo de tipo intermedio. CONCLUSIONES: Los portadores del alelo A del SNP rs4864548A/G presentarían un mayor potencial de sufrir problemas asociados a la obesidad, pero es necesario realizar estudios con poblaciones más grandes y con mejor paridad de género, que permita corroborar esta aseveración


BACKGROUND: Nutritional status may be affected by eating behavior and circadian rhythms. These are regulated by the CLOCK gene, whose T alleles of SNP rs3749474T / C and A of SNP rs4864548A / G, have been associated with obesity in adults. METHODS: 65 subjects were evaluated using the real-time PCR technique to determine whether they were carriers of the T allele of the SNP rs3749474T/C or the A of the SNP rs4864548A/G. Anthropometric measurements were made, and the TFEQ and Horne-Östberg questionnaires were applied. RESULTS: Of the 65 subjects studied, 8 were carriers of the T allele of the SNP rs3749474T / C and 7 of the A of the SNP rs4864548A/G. The carriers of the A allele had higher average BMI values (26.58), waist circumference (89.57cm) and fat percentage (31.56%), with no statistically significant differences between them. No statistically significant differences were found regarding eating behavior. 66.67% of the total subjects presented an intermediate type chronotype. CONCLUSIONS: The carriers of the A allele of SNP rs4864548A/G would have a greater potential to suffer problems associated with obesity, but studies with larger populations and with better gender parity are necessary, which allows to confirm this assertion


Assuntos
Humanos , Masculino , Feminino , Avaliação Nutricional , Estado Nutricional/fisiologia , Polimorfismo Genético/fisiologia , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/análise , Polimorfismo de Nucleotídeo Único/genética , Obesidade/genética , Ritmo Circadiano/fisiologia , Chile/epidemiologia , Comportamento Alimentar , Estudantes/estatística & dados numéricos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Pesos e Medidas Corporais/estatística & dados numéricos
5.
Pharm Res ; 37(3): 44, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31993760

RESUMO

PURPOSE: This prospective study aimed to evaluate the effects of genetic polymorphisms in sulindac-related metabolizing enzyme genes including FMO3 and AOX1 on the population pharmacokinetics of sulindac in 58 pregnant women with preterm labor. METHODS: Plasma samples were collected at 1.5, 4, and 10 h after first oral administration of sulindac. Plasma concentrations of sulindac and its active metabolite (sulindac sulfide) were determined, and pharmacokinetic analysis was performed with NONMEM 7.3. RESULTS: The mean maternal and gestational ages at the time of dosing were 32.5 ± 4.4 (range, 20-41) years and 27.4 ± 4.4 (range, 16.4-33.4) weeks, respectively. In the population pharmacokinetic analysis, one depot compartment model of sulindac with absorption lag time best described the data. The metabolism of sulindac and sulindac sulfide was described using Michaelis-Menten kinetics. In stepwise modeling, gestational age impacted volume of distribution (Vc), and FMO3 rs2266782 was shown by the Michaelis constant to affect conversion of sulindac sulfide to sulindac (KM32); these were retained in the final model. CONCLUSIONS: Genetic polymorphisms of FMO3 and AOX1 could affect the pharmacokinetics of sulindac in women who undergo preterm labor. The results of this study could help clinicians develop individualized treatment plans for administering sulindac.


Assuntos
Aldeído Oxidase/genética , Anti-Inflamatórios/farmacocinética , Trabalho de Parto Prematuro/metabolismo , Oxigenases/genética , Polimorfismo Genético/fisiologia , Sulindaco/farmacocinética , Adulto , Aldeído Oxidase/metabolismo , Feminino , Genótipo , Idade Gestacional , Humanos , Modelos Biológicos , Oxigenases/metabolismo , Gravidez , Estudos Prospectivos , Transdução de Sinais , Sulindaco/análogos & derivados , Sulindaco/metabolismo
6.
Insect Sci ; 27(3): 583-612, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30456932

RESUMO

Polymorphisms for melanic form of insects may provide various selective advantages. However, melanic alleles may have significant/subtle pleiotrophic "costs." Several potential pleiotrophic effects of the W (=Y)-linked melanism gene in Papilio glaucus L. (Lepidoptera) showed no costs for melanic versus yellow in adult size, oviposition preferences, fecundity, egg viability, larval survival/growth rates, cold stress tolerance, or postdiapause emergence times. Sexual selection (males choosing yellow rather than mimetic dark females) had been suggested to provide a balanced polymorphism in P. glaucus, but spermatophore counts in wild females and direct field tethering studies of size-matched pairs of virgin females (dark and yellow), show that male preferences are random or frequency-dependent from Florida to Michigan, providing no yellow counter-advantages. Recent frequency declines of dark (melanic/mimetic) females in P. glaucus populations are shown in several major populations from Florida (27.3°N latitude) to Ohio (38.5° N). Summer temperatures have increased significantly at all these locations during this time (1999-2018), but whether dark morphs may be more vulnerable (in any stage) to such climate warming remains to be determined. Additional potential reasons for the frequency declines in mimetic females are discussed: (i) genetic introgression of Z-linked melanism suppressor genes from P. canadensis (R & J) and the hybrid species, P. appalachiensis (Pavulaan & Wright), (ii) differential developmental incompatibilities, or Haldane effects, known to occur in hybrids, (iii) selection against intermediately melanic ("dusty") females (with the W-linked melanic gene, b+) which higher temperatures can cause.


Assuntos
Borboletas , Frequência do Gene , Melanose/genética , Animais , Ecologia , Feminino , Aquecimento Global , Fenótipo , Polimorfismo Genético/fisiologia
7.
Evolution ; 74(1): 15-28, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31520540

RESUMO

Hamilton's idea that haplodiploidy favors the evolution of altruism-the haplodiploidy hypothesis-relies on the relatedness asymmetry between the sexes caused by the sex-specific ploidies. Theoretical work on the consequences of relatedness asymmetries has significantly improved our understanding of sex allocation and intracolony conflicts, but the importance of haplodiploidy for the evolution of altruism came to be seen as minor. However, recently it was shown that haplodiploidy can strongly favor the evolution of eusociality, provided additional "preadaptations" are also present, such as the production of multiple broods per season and maternal ability to bias offspring sex ratios. These results were obtained assuming no influence of workers on the sex ratio, even though worker control of the sex ratio is known to occur. Here, we model the evolution of sex-specific fratricide as a mechanism of worker control over the sex ratio. We show that fratricide can facilitate the initial evolution of helping. However, fratricide can also hamper the evolution of unconditional help. Instead, social polymorphism evolves a mixture of helping and dispersing offspring. Finally, we show that the co-evolution of sex-allocation strategies of workers (fratricide) and queens leads to a split production of the sexes, with some colonies specializing in males and others in females. Thus, the model predicts that fratricide spawns a diversity of co-existing life cycles that strongly vary in degree of sociality and sex ratios.


Assuntos
Evolução Biológica , Himenópteros/fisiologia , Traços de História de Vida , Polimorfismo Genético/fisiologia , Animais , Himenópteros/genética , Modelos Biológicos , Fatores Sexuais , Razão de Masculinidade , Comportamento Social
8.
Physiol Res ; 68(Suppl 1): S59-S64, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31755291

RESUMO

The aim of this study was to evaluate the association between OPRM1 and ABCB1 polymorphisms on pain relief with epidural sufentanil in 69 patients after rectosigma resection for cancer. The median number of injections (SD) 2.31 (1.36), IQR=1, required by 118AA subjects was significantly lower in comparison with 118AG group 5.25 (3.13), IQR=6.5, (chi(2)=9.75, p=0.001); correspondingly median drug consumption of 1.16 (0.79), IQR=1.083, defined daily doses (DDD) was significantly less in the 118AA group in comparison with 2.14 (1.17), IQR=2.23, DDD in 118AG subjects, (chi(2)=7.00, p=0.008). Opioid-induced adverse effects were observed in 15 % and 33 % of patients in 118AA and 118AG groups, respectively (chi(2)=8.16, p=0.004). The median number of injections (SD) required by women and men was 3.30 (2.16), IQR=2, and 2.80 (1.59), IQR=1, respectively (chi(2)=6.25, p=0.012). Opioid-induced adverse effects were observed in 26 % and 12 % of women and men, respectively (chi(2)=5.49, p=0.011). Heterozygotes of OPRM1 polymorphism and women were more difficult to treat subpopulations that required higher doses of rescue analgesic medication and suffered more adverse effects.


Assuntos
Analgesia Epidural/métodos , Manejo da Dor/métodos , Polimorfismo Genético/fisiologia , Receptores Opioides mu/genética , Sufentanil/administração & dosagem , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Idoso , Idoso de 80 Anos ou mais , Analgésicos Opioides/administração & dosagem , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/tratamento farmacológico , Estudos Prospectivos
9.
Proc Biol Sci ; 286(1912): 20191879, 2019 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-31594509

RESUMO

Intraspecific colour polymorphisms have been the focus of numerous studies, yet processes affecting melanism in the marine environment remain poorly understood. Arguably, the most prominent example of melanism in marine species occurs in manta rays (Mobula birostris and Mobula alfredi). Here, we use long-term photo identification catalogues to document the frequency variation of melanism across Indo-Pacific manta ray populations and test for evidence of selection by predation acting on colour morph variants. We use mark-recapture modelling to compare survivorship of typical and melanistic colour morphs in three M. alfredi populations and assess the relationship between frequency variation and geographical distance. While there were large differences in melanism frequencies among populations of both species (0-40.70%), apparent survival estimates revealed no difference in survivorship between colour morphs. We found a significant association between phenotypic and geographical distance in M. birostris, but not in M. alfredi. Our results suggest that melanism is not under selection by predation in the tested M. alfredi populations, and that frequency differences across populations of both species are a consequence of neutral genetic processes. As genetic colour polymorphisms are often subjected to complex selection mechanisms, our findings only begin to elucidate the underlying evolutionary processes responsible for the maintenance and frequency variation of melanism in manta ray populations.


Assuntos
Pigmentação/genética , Polimorfismo Genético/fisiologia , Rajidae/genética , Animais , Cor
10.
Medicina (Kaunas) ; 55(6)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195645

RESUMO

Background and Objectives: Studies suggest that FAS/FASL polymorphisms are associated with male infertility; however, their results are still inconclusive. Therefore, this systematic review and meta-analysis aimed to summarize and clarify the overall association of FAS/FASL polymorphisms and risk of male infertility. Materials and Methods: Our search was conducted on the databases of Science Direct, PubMed and Google Scholar. For performing the meta-analysis, pooled odds ratio (OR) values with 95% confidence interval (CI) was applied in order to analyze the strength of association between the FAS/FASL polymorphisms and risk of male infertility. A total of seven relevant studies published up to September 2018 were considered. Results: FASL-844C/T genotype results of 559 patients and 623 healthy individuals were included in our study. For FAS-670A/G genotype effect, 751 patients and 821 healthy individuals were explored. Results showed that all analysis models including dominant, recessive and allelic models of FASL-844C/T and FAS-670A/G polymorphism had no significant effect on infertility in men (p > 0.05 and p > 0.05, respectively). According to sensitivity analysis, our results were stable. Conclusion: We demonstrated that FAS/FASL polymorphisms might not be an effective factor on male reproductive health. For precise determination of FAS/FASL polymorphisms effects on male infertility, large-scale case-control studies should be performed.


Assuntos
Proteína Ligante Fas/análise , Infertilidade Masculina/genética , Polimorfismo Genético/fisiologia , Receptor fas/análise , Proteína Ligante Fas/sangue , Predisposição Genética para Doença , Humanos , Masculino , Fatores de Risco , Receptor fas/sangue
11.
Medicina (Kaunas) ; 55(6)2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185683

RESUMO

BACKGROUND AND OBJECTIVES: The ACE gene encodes the angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system. Increased ACE activity may cause abnormal regulation of placental circulation and angiogenesis, resulting in adverse pregnancy outcomes. Previous studies have reported that the insertion/deletion (I/D) polymorphism of the ACE gene is associated with the development of preterm birth (PTB). However, results of the association between ACE gene I/D and PTB are inconsistent in various populations. Therefore, we performed a case-control study and a meta-analysis to evaluate the association between ACE I/D polymorphism and PTB. Materials and Methods: We analyzed a total of 254 subjects (111 patients with PTB and 143 women at ≥38 weeks gestation) for the case-control study. For the meta-analysis, we searched Google Scholar, PubMed, and NCBI databases with the terms "ACE," "angiotensin-converting enzyme," "preterm birth," "preterm delivery," and their combinations. Results: Our results of the case-control study indicated that ACE I/D polymorphism is significantly associated with PTBs in the overdominant genetic model (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.347-0.949, p = 0.029) and that the ID genotype of ACE I/D polymorphism has a protective effect for PTB (OR 0.57, 95% CI 0.333-0.986, p = 0.043). Similarly, the meta-analysis showed that the OR for the ACE gene ID genotype was 0.66 (95% CI 0.490-0.900, p < 0.01). Conclusion: The ACE gene ID genotype has a significant association with PTB and is a protective factor for PTB. A larger sample set and functional studies are required to further elucidate of our findings.


Assuntos
Peptidil Dipeptidase A/análise , Nascimento Prematuro/sangue , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/epidemiologia , Humanos , Recém-Nascido , Razão de Chances , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/genética , Polimorfismo Genético/fisiologia , Nascimento Prematuro/epidemiologia , República da Coreia/epidemiologia
12.
Medicina (Kaunas) ; 55(5)2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31121922

RESUMO

Background and Objectives: Vitamin D levels have been associated with a diversity of diseases, including obesity. Vitamin D presents a pleiotropic action, and can regulate insulin secretion and inflammatory responses. Vitamin D receptor (VDR) gene polymorphisms are involved in the gene expression regulation and have been associated with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the association between the polymorphisms ApaI (rs7975232), BsmI (rs1544410), FokI (rs10735810), and TaqI (rs731236) in the VDR gene in people diagnosed with T2DM, and plasma 25-hydroxivitamin D levels [25(OH)D]. Materials and Methods: A total of 101 T2DM patients and 62 gender, age, and body mass index (BMI) matched non-diabetic controls were included in this study. Molecular analyzes were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The plasma 25(OH)D levels were measured by high performance liquid chromatography. Results: The plasma 25(OH)D levels were lower in T2DM patients (17.2 (16.6) ng/mL) when compared with the control subjects (30.8 (16.2) ng/mL, p < 0.0001), independently of obesity status. We found no difference between genotypic and allelic frequencies of the VDR polymorphisms when comparing the T2DM group and control group (p > 0.05 for all), and did not show any association with plasma 25(OH)D levels. Conclusions: These results suggest that T2DM is associated with lower plasma 25(OH)D levels, which are not related to BMI and VDR gene polymorphisms.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Polimorfismo Genético/fisiologia , Receptores de Calcitriol/genética , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/genética , Adulto , Idoso , Glicemia/análise , Brasil , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Jejum/sangue , Feminino , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Receptores de Calcitriol/análise , Receptores de Calcitriol/sangue , Estatísticas não Paramétricas , Vitamina D/análise , Vitamina D/sangue , Deficiência de Vitamina D/sangue
13.
Appetite ; 140: 142-150, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31095973

RESUMO

The regulation of appetite is supported by dopamine-modulated brain circuits. Recent studies have shown that transcranial direct current stimulation (tDCS) aimed at increasing the excitability of the dorsolateral prefrontal cortex can reduce appetite, but the underlying mechanisms remain unknown, and response variability is large. The aim of this study was to determine whether individual differences in Catechol-O-methyl transferase (COMT) Val158Met polymorphism can influence tDCS effects on appetite. Thirty-eight adult women with obesity, classified as carriers or non-carriers of the Met allele, underwent a randomized, double-blind, sham-controlled tDCS intervention involving three phases: Phase I, target engagement (immediate effects of tDCS on working memory performance), Phase II, tDCS only (10 sessions, two weeks), and Phase III, tDCS + hypocaloric diet: (6 sessions, two weeks, 30% energy intake reduction, inpatient). Data were analyzed using linear mixed-effects models and mixed ANCOVA. Appetite was evaluated using visual analogue scales. We found that Met-carriers receiving active tDCS were the only participants who experienced a significant reduction of appetite over time. Conversely, Met non-carriers maintained high levels of appetite during the intervention; this effect was driven by a delayed paradoxical rise in appetite after stimulation. Working memory task performance at phase I correlated with subsequent appetite change in a COMT-dependent manner: speed improvements during the task predicted appetite increase in Met carriers and appetite reduction in Met non-carriers. Our findings suggest that genotype differences impacting dopamine levels influence prefrontal tDCS effects on appetite. This source of variability should be considered in the design of future studies.


Assuntos
Apetite/genética , Catecol O-Metiltransferase/genética , Obesidade/genética , Polimorfismo Genético/fisiologia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Dieta Redutora , Método Duplo-Cego , Ingestão de Energia/genética , Feminino , Genótipo , Humanos , Obesidade/fisiopatologia , Obesidade/psicologia , Córtex Pré-Frontal/fisiopatologia , Adulto Jovem
14.
J Neuroendocrinol ; 31(4): e12692, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30712287

RESUMO

In patients with growth hormone (GH) deficiency (GHD), low doses of recombinant human GH (rhGH) have a similar or better long-term clinical effect than higher doses. Pharmacogenetic studies suggest that GH receptor (GHR) polymorphism only influences some metabolic parameters. Nonetheless, there is no clear scientific evidence proving the effects of lower rhGH dose regimens on metabolic parameters. The aim of our prospective study was to evaluate the effects of GHR polymorphism in adult GHD patients treated with low rhGH dose during short- (6 and 12 months) and long-term (5 years) follow-up. Sixty-nine GHD adult patients were studied, before and during treatment with rhGH, using a standardised low-dose protocol calculated on the basis of body weight (0.01-0.03 mg kg-1  week-1 ) and monitored by an insulin-like growth factor (IGF)-I plasma assay, as well as anthropometric and metabolic parameters. The GHR genotype (flfl, fld3 or d3d3) was determined from the peripheral blood. d3-GHR carriers showed a more effective short- and long-term response to low rhGH dose with respect to low-density lipoprotein reduction, body composition and blood pressure (homozygous patients only); d3-GHR homozygosity is related to a significant IGF-I increase during short-term follow-up. Regression analysis demonstrated that rhGH dose, age at diagnosis and GHR genotype are the major determinants of IGF-I increase at 6 and 12 months of replacement therapy. The d3d3-GHR genotype may influence some metabolic effects during the short- and long-term follow-up of low rhGH dose and could be an independent determinant of the increase of IGF- I during short-term follow-up.


Assuntos
Hormônio do Crescimento Humano/administração & dosagem , Hormônio do Crescimento Humano/deficiência , Polimorfismo Genético/genética , Receptores da Somatotropina/genética , Receptores da Somatotropina/fisiologia , Proteínas Recombinantes/administração & dosagem , Adulto , Idoso , Feminino , Genótipo , Terapia de Reposição Hormonal , Humanos , Fator de Crescimento Insulin-Like I/análise , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/fisiologia , Estudos Prospectivos
15.
Vet Med Sci ; 5(2): 157-161, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30735014

RESUMO

Melatonin is the main hormone of seasonal breeding in sheep and goat which has an effect on reproductive organs via its receptors. Studies have shown that mutations in melatonin receptor 1A (MTNR1A) gene are related to litter size as well as the ovulation rate in sheep and goats. In this study, polymorphism of two loci in MTNR1A melatonin receptor gene was studied in order to survey their relationship with litter size in Markhoz goats. PCR primers were employed to mask polymorphisms of MTNR1A in 150 does by PCR-RFLP method. After DNA extraction, the PCR-RFLP was performed using Ecol31I and HpaI restriction enzymes. Results showed that these loci were not polymorphic. These results show that the fecundity of Markhoz goats is not linked to MTNR1A. No polymorphism in MTNR1A was found in Markhoz goats, therefore, it is essential to test polymorphism of other genes or loci to facilitate marker-assisted selection techniques to improve reproduction traits in Markhoz goats.


Assuntos
Fertilidade/genética , Cabras/fisiologia , Tamanho da Ninhada de Vivíparos/genética , Polimorfismo Genético/fisiologia , Receptor MT1 de Melatonina/genética , Animais , Feminino , Cabras/genética , Receptor MT1 de Melatonina/metabolismo
16.
Inflammopharmacology ; 27(3): 453-464, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30756223

RESUMO

Studies have demonstrated that susceptibility to type 2 diabetes (T2D) is influenced by common polymorphism in the zinc transporter 8 gene SLC30A8, providing novel insight into the role of zinc in diabetes. Intriguingly, zinc participates in every step of the process, including insulin synthesis, crystallization, storage, secretion and signaling. Zinc deficiency or overload is associated with various disorders, such as diabetes, cardiovascular disease and obesity. Zinc supplementation is considered as an effective means of treating or preventing T2D in people with certain SLC30A8 genotypes. Three important protein families-zinc transporters (ZnTs), zinc importers (ZiPs) and metallothionein (MT)-participate in maintaining zinc homeostasis. Here, we review research on the physiological characteristics of zinc and its role in the pancreas and homeostasis regulation mechanisms, along with the latest research on the structure and function of ZnT/ZiP and MT. In addition, we summarize the advancements in research on SLC30A8 gene polymorphism in search of a mechanism to explain the relationship between the R risk allele and zinc transporter activity.


Assuntos
Pâncreas/metabolismo , Zinco/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Homeostase/fisiologia , Humanos , Pâncreas/patologia , Polimorfismo Genético/fisiologia , Transdução de Sinais/fisiologia
17.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(2): 90-98, feb. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-175800

RESUMO

Introduction: Increasing number of experimental and clinical studies suggest a strong relationship between hyperglycemia, oxidative stress, DNA damage and diabetic nephropathy (DN). Also, epidemiologic studies remark an enhanced risk of cancer with type 2 diabetes. This research aims to assess whether the X-ray cross complementing group 3 (XRCC3) gene T241M polymorphism (rs861539) and X-ray cross complementing group 1 (XRCC1) gene A399G polymorphism (rs25487) are related with predisposition to type 2 diabetes mellitus (T2DM) and to diabetic nephropathy in Turkish population. Materials and methods: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was performed to identify the distribution of genotypes and frequency of alleles of T241M polymorphism of the XRCC3 gene (XRCC3 T241M) and A399G polymorphism of the XRCC1 gene (XRCC1 A399G). The study population included 238 subjects residing in Istanbul, Turkey; 116 with T2DM, 50 with DN and 72 with normal glucose metabolism. Results and conclusion: Polymorphic Gln allele of XRCC1 gene was significantly related with T2DM and DN (OR 3.09, 95% CI 1.14-8.40 and OR 3.29 95% CI 1.23-8.80, respectively) however, there was no statistical association of XRCC3 T241M with T2DM or DN. The results of this study suggest that XRCC1 399Gln polymorphism is related with an increased susceptibility to T2DM and DN in the studied Turkish population


Introducción: Un número creciente de estudios experimentales y clínicos sugiere una sólida relación entre hiperglucemia, estrés oxidativo, daño en el ADN y nefropatía diabética (ND). Además, los estudios epidemiológicos advierten mayor riesgo de cáncer con diabetes de tipo 2. Esta investigación tiene como objetivo evaluar si el polimorfismo del gen T241M del grupo 3 (XRCC3) complementario cruzado de rayos X (rs861539) y el polimorfismo del gen A399G del grupo 1 (XRCC1) complementario cruzado de rayos X (rs25487) están relacionados con la predisposición a la diabetes mellitus de tipo 2 (DM2) y a la nefropatía diabética en la población turca. Materiales y métodos: Se realizó un polimorfismo de longitud de fragmento de restricción basado en la reacción en cadena de la polimerasa (PCR-RFLP) para identificar la distribución de genotipos y la frecuencia de los alelos del polimorfismo T241M del gen XRCC3 (XRCC3 T241M) y el polimorfismo A399G del gen XRCC1(XRCC1 A399G). La población de estudio incluyó a 238 individuos que residían en Estambul, Turquía; 116 de ellos con DM2, 50 con ND y 72 con metabolismo de la glucosa normal. Resultados y conclusión: El alelo Gln polimórfico del gen XRCC1 se relacionó de manera importante con DM2 y ND (OR: 3,09; IC95%: 1,14-8,40 y OR: 3,29; IC95%:1,23-8,80, respectivamente). Sin embargo, no hubo asociación estadística de XRCC3 T241M con DM2 o ND. Los resultados de este estudio sugieren que el polimorfismo XRCC1 399Gln está relacionado con un aumento de la susceptibilidad a la DM2 y a la ND en la población turca estudiada


Assuntos
Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/genética , Neuropatias Diabéticas/genética , Reparo do DNA/fisiologia , Polimorfismo de Fragmento de Restrição/genética , Polimorfismo Genético/genética , Polimorfismo Genético/fisiologia , Turquia , Polimorfismo de Fragmento de Restrição/fisiologia , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/diagnóstico
18.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(2): 99-107, feb. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-175801

RESUMO

Background: Type 2 diabetes mellitus (T2DM) is an inflammatory condition associated to obesity and increased oxidative stress. Haptoglobin (Hp) is an acute phase reactant that scavenges extracorpuscular hemoglobin from circulation and prevents heme-iron oxidative damage. Objective: To assess the association between Hp levels and Hp1-Hp2 gene polymorphism and clinical and laboratory parameters in patients with T2DM. Methods: The study sample consisted of 102 T2DM patients and 62 controls. Hp plasma levels were measured using an ELISA assay, and Hp genotyping was performed using a specific two-step allelic polymerase chain reaction. Results: Hp levels were higher in T2DM patients as compared to controls (p=0.005). T2DM patients with high blood pressure had higher Hp levels than patients without this comorbidity (p=0.021). Obese T2DM patients had higher Hp levels as compared to obese controls (p=0.009) and to non-obese T2DM patients (p=0.003). The Hp1-Hp1 genotype was showed to be associated to T2DM according to additive (OR=3.038, 95% CI 1.127-8.192; p=0.036) and dominant model (OR=0.320, 95% CI 0.118-0.839; p=0.010), but Hp2 allele carriers contributed with higher Hp levels in T2DM as compared to controls. Waist circumference (p=0.002), BMI (p=0.001), and IL-6 (p=0.012), and hs-CRP (p=0.001) levels positively correlated with Hp levels in the T2DM group. Conclusion: These results suggest that Hp levels are influenced by Hp1-Hp2 polymorphism, obesity, inflammatory status, and high blood pressure in T2DM


Antecedentes: La diabetes mellitus tipo 2 (DM2) es una afección inflamatoria asociada con la obesidad y el aumento del estrés oxidativo. La haptoglobina (Hp) es un reactante de fase aguda que elimina la hemoglobina extracorpuscular de la circulación y previene el daño oxidativo del hierro hemo. Objetivo: Evaluar la asociación entre los niveles de Hp y el polimorfismo del gen Hp1-Hp2, y los parámetros clínicos y de laboratorio en individuos con DM2. Métodos: Ciento dos pacientes con DM2 y 62 controles se incluyeron en este estudio. Los niveles plasmáticos de Hp se cuantificaron por ELISA y el genotipado de Hp se llevó a cabo mediante una PCR alelo-específica en dos pasos. Resultados: Los niveles de Hp fueron más altos en pacientes con DM2 en comparación con los controles (p=0,005). Los pacientes con DM2 con hipertensión arterial mostraron niveles más altos de Hp en comparación con los pacientes sin hipertensión (p=0,021). Los pacientes obesos con DM2 mostraron niveles más altos de Hp en comparación con los controles obesos (p=0,009) y con los pacientes con DM2 no obesos (p=0,003). El genotipo Hp1-Hp1 mostró asociación con DM2 según el modelo aditivo (OR=3,038; IC 95%: 1,127-8,192; p=0,036) y el modelo dominante (OR=0,320; IC 95%: 0,118-0,839; p=0,010), pero entre los portadores del alelo Hp2, las concentraciones de Hp eran más altas en T2DM que en controles. La circunferencia de la cintura (p=0,002), el IMC (p=0,001), IL-6 (p=0,012) y la hs-CRP (p=0,001) se correlacionaron positivamente con los niveles de Hp en el grupo DM2. Conclusión: Estos resultados sugieren que los niveles de Hp están influenciados por el polimorfismo Hp1-Hp2, la obesidad, el estado inflamatorio y la hipertensión en DM2


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Haptoglobinas/fisiologia , Polimorfismo Genético/genética , Haptoglobinas/análise , Haptoglobinas/genética , Polimorfismo Genético/fisiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Inflamação/fisiopatologia , Hipertensão/fisiopatologia , Obesidade/fisiopatologia , Brasil , Estudos de Casos e Controles , Estudos Transversais , Genoma Humano/fisiologia
19.
Mech Ageing Dev ; 178: 33-40, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30633899

RESUMO

Klotho gene polymorphisms have been implicated in healthy aging, but inconsistences in findings from previous case-control studies have raised concerns regarding the associations between KLOTHO gene polymorphisms and susceptibility to aging-related diseases and longevity. Hence, this meta-analysis was performed. We assessed the associations between two polymorphisms (G-395 A/rs1207568 and F352 V/rs9536314) and five parameters (urolithiasis, cognitive impairment, cardiovascular disease, cancer, and longevity) by calculating pooled odds ratios with 95% confidence intervals. According to the pooled results, the G allele of the G-395 A polymorphism conferred a significantly higher risk of urolithiasis; G-395 A was related to the susceptibility to cardiovascular disease under allele, dominant, and recessive models. There was no significant association between the G-395 A polymorphism and cognitive impairment among the elderly. The F allele of the F352 V polymorphism protected against breast and ovarian cancer susceptibility. Interestingly, based on the results of the subgroup analysis, the F352 V polymorphism was associated with the overall risk of neoplasms in BRCA1 mutation carriers but not in BRCA2 mutation carriers. Moreover, the F allele played a protective role in determining human longevity. In conclusion, Klotho G-395 A polymorphisms were associated with urolithiasis and cardiovascular disease but not with cognitive impairment. Additionally, Klotho F352 V polymorphisms were associated with cancers and longevity.


Assuntos
Glucuronidase/fisiologia , Envelhecimento Saudável/genética , Longevidade/genética , Polimorfismo Genético/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/genética , Doenças Cardiovasculares/genética , Estudos de Casos e Controles , Disfunção Cognitiva/genética , Feminino , Glucuronidase/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Urolitíase/genética
20.
Med Sci (Paris) ; 35(12): 1130-1136, 2019 Dec.
Artigo em Francês | MEDLINE | ID: mdl-31903927

RESUMO

Therapeutic antibodies have been increasingly used for the treatment of various diseases, including cancers and chronic inflammatory diseases. The pharmacokinetic interindividual variability of mAbs is large and influences, at least in part, the clinical response to antibody treatment. This variability is explained by a number of individual sources of variability, which are reviewed here. Some of them are major because they are frequently reported to greatly influence the interindividual variability; notably, increased body size, the presence of anti-drug antibodies, and high antigen mass are associated with decreased antibody concentrations. Other individual sources of variability are of less critical importance. They include sex, age, co-treatments, or genetic polymorphisms of IgG Fc receptors (FcgRs). The interindividual variability of antibody pharmacokinetics should be soundly described in order to design optimal dosing strategy.


Assuntos
Anticorpos Monoclonais/farmacocinética , Individualidade , Fatores Etários , Anticorpos Monoclonais/uso terapêutico , Biomarcadores Farmacológicos/análise , Comorbidade , Relação Dose-Resposta Imunológica , Feminino , Humanos , Masculino , Testes Farmacogenômicos , Polimorfismo Genético/fisiologia , Medicina de Precisão/métodos , Fatores Sexuais
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