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1.
Braz J Med Biol Res ; 57: e13257, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38958362

RESUMO

Rivaroxaban is a direct factor Xa inhibitor. Its interindividual variability is large and may be connected to the occurrence of adverse drug reactions or drug inefficacy. Pharmacogenetics studies concentrating on the reasons underlying rivaroxaban's inadequate response could help explain the differences in treatment results and medication safety profiles. Against this background, this study evaluated whether polymorphisms in the gene encoding the ABCG2 transporter modify the pharmacokinetic characteristics of rivaroxaban. A total of 117 healthy volunteers participated in two bioequivalence experiments with a single oral dose of 20 mg rivaroxaban, with one group fasting and the other being fed. Ultra-high-performance liquid chromatography coupled with mass spectrometry was employed to determine the plasma concentrations of rivaroxaban, and the WinNonlin program was used to calculate the pharmacokinetics parameters. In the fasting group, the rivaroxaban pharmacokinetic parameters of Vd (508.27 vs 334.45 vs 275.59 L) and t1/2 (41.04 vs 16.43 vs 15.47 h) were significantly higher in ABCG2 421 A/A genotype carriers than in ABCG2 421 C/C and 421 C/A genotype carriers (P<0.05). The mean values of Cmax (145.81 vs 176.27 vs 190.19 ng/mL), AUC0-t (1193.81 vs 1374.69 vs 1570.77 ng/mL·h), and Cl (11.82 vs 14.50 vs 13.01 mL/h) for these groups were lower, but this difference was not statistically significant (P>0.05). These findings suggested that the ABCG2 421 A/A genotype may impact rivaroxaban parameters after a single dose in healthy subjects. This finding must be validated before it is applied in clinical practice.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Inibidores do Fator Xa , Genótipo , Voluntários Saudáveis , Proteínas de Neoplasias , Rivaroxabana , Humanos , Rivaroxabana/farmacocinética , Rivaroxabana/administração & dosagem , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Masculino , Inibidores do Fator Xa/farmacocinética , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/sangue , Adulto , Feminino , Adulto Jovem , Proteínas de Neoplasias/genética , Cromatografia Líquida de Alta Pressão , Polimorfismo Genético , Equivalência Terapêutica , Área Sob a Curva
2.
Acta Dermatovenerol Croat ; 32(1): 1-6, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38946181

RESUMO

BACKGROUND: The pro-inflammatory adipokine resistin is known to be related to obesity, insulin resistance, and inflammation. Resistin's significance in the etiology of inflammatory illnesses, such as psoriasis, is explored herein. We examined the link between resistin gene polymorphisms (-420 C>G and +299 G>A) and psoriasis in the Turkish population. METHODS: In this study, we examined 107 patients with psoriasis and 103 healthy controls. Resistin -420 C>G (rs1862513) and +299 G>A (rs3745367) gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In patients with psoriasis, the frequency of the resistin -420 CG genotype was meaningfully lower than in the controls. In comparison with the controls, the resistin +299 GA genotype and A allele frequencies were significantly higher. The Resistin -420 CG genotype significantly reduced the risk of psoriasis incidence, while the resistin +299 GA genotype and A allele were found to be associated with a higher risk of psoriasis. CONCLUSIONS: In the Turkish community, resistin gene polymorphisms at -420 C>G and +299 G>A may exert an important influence on psoriasis etiology and susceptibility.


Assuntos
Predisposição Genética para Doença , Psoríase , Resistina , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Psoríase/genética , Resistina/genética , Turquia
3.
Ren Fail ; 46(2): 2376930, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38982880

RESUMO

Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.


Assuntos
Arildialquilfosfatase , Estresse Oxidativo , Insuficiência Renal Crônica , Arildialquilfosfatase/metabolismo , Arildialquilfosfatase/genética , Arildialquilfosfatase/sangue , Humanos , Insuficiência Renal Crônica/complicações , Biomarcadores/sangue , Polimorfismo Genético , Doenças Cardiovasculares/etiologia , Transplante de Rim , Aterosclerose/etiologia , Prognóstico
4.
Biochemistry (Mosc) ; 89(6): 1002-1013, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38981696

RESUMO

Currently, numerous associations between genetic polymorphisms and various diseases have been characterized through the Genome-Wide Association Studies. Majority of the clinically significant polymorphisms are localized in non-coding regions of the genome. While modern bioinformatic resources make it possible to predict molecular mechanisms that explain influence of the non-coding polymorphisms on gene expression, such hypotheses require experimental verification. This review discusses the methods for elucidating molecular mechanisms underlying dependence of the disease pathogenesis on specific genetic variants within the non-coding sequences. A particular focus is on the methods for identification of transcription factors with binding efficiency dependent on polymorphic variations. Despite remarkable progress in bioinformatic resources enabling prediction of the impact of polymorphisms on the disease pathogenesis, there is still the need for experimental approaches to investigate this issue.


Assuntos
Genoma Humano , Polimorfismo Genético , Humanos , Estudo de Associação Genômica Ampla , Sequências Reguladoras de Ácido Nucleico , Biologia Computacional/métodos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
5.
Sci Rep ; 14(1): 15873, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982272

RESUMO

Apolipoprotein E (APOE) is a major cholesterol carrier responsible for lipid transport and injury repair in the brain. The human APOE gene (h-APOE) has 3 naturally occurring alleles: ε3, the common allele; ε4, which increases Alzheimer's disease (AD) risk up to 15-fold; and ε2, the rare allele which protects against AD. Although APOE4 has negative effects on neurocognition in old age, its persistence in the population suggests a survival advantage. We investigated the relationship between APOE genotypes and fertility in EFAD mice, a transgenic mouse model expressing h-APOE. We show that APOE4 transgenic mice had the highest level of reproductive performance, followed by APOE3 and APOE2. Intriguingly, APOE3 pregnancies had more fetal resorptions and reduced fetal weights relative to APOE4 pregnancies. In conclusion, APOE genotypes impact fertility and pregnancy outcomes in female mice, in concordance with findings in human populations. These mouse models may help elucidate how h-APOE4 promotes reproductive fitness at the cost of AD in later life.


Assuntos
Doença de Alzheimer , Apolipoproteínas E , Modelos Animais de Doenças , Fertilidade , Camundongos Transgênicos , Animais , Doença de Alzheimer/genética , Feminino , Camundongos , Fertilidade/genética , Humanos , Apolipoproteínas E/genética , Apolipoproteína E4/genética , Polimorfismo Genético , Gravidez , Genótipo , Apolipoproteína E3/genética , Alelos
6.
Genome Biol Evol ; 16(7)2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38934859

RESUMO

During evolution, new open reading frames (ORFs) with the potential to give rise to novel proteins continuously emerge. A recent compilation of noncanonical ORFs with translation signatures in humans has identified thousands of cases with a putative de novo origin. However, it is not known which is their distribution in the population. Are they universally translated? Here, we use ribosome profiling data from 65 lymphoblastoid cell lines from individuals of Yoruba origin to investigate this question. We identify 2,587 de novo ORFs translated in at least one of the cell lines. In line with their de novo origin, the encoded proteins tend to be smaller than 100 amino acids and encode positively charged proteins. We observe that the de novo ORFs are more polymorphic in the population than the set of canonical proteins, with a substantial fraction of them being translated in only some of the cell lines. Remarkably, this difference remains significant after controlling for differences in the translation levels. These results suggest that variations in the level translation of de novo ORFs could be a relevant source of intraspecies phenotypic diversity in humans.


Assuntos
Fases de Leitura Aberta , Polimorfismo Genético , Humanos , Biossíntese de Proteínas , Linhagem Celular , Evolução Molecular , Ribossomos/genética , Ribossomos/metabolismo
7.
Medicina (Kaunas) ; 60(6)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38929507

RESUMO

Background: Preeclampsia (PE) is a critical condition affecting pregnancies worldwide. Understanding its etiology, particularly the genetic factors, is vital. This study aims to investigate the association between ACE gene polymorphisms, specifically the ACE G2350A (rs4343) variant, and the predisposition to PE, offering insights into the genetic predisposition towards this complex condition. Methods: A case-control study was conducted with 140 participants without PE (Control Group) and 128 participants diagnosed with PE (PE Group). The study focused on comparing the prevalence of the rs4343 polymorphism between the groups. Results: The analysis identified a significantly reduced risk associated with the AG genotype and an insignificant increase in risk with the AA genotype. Statistically significant differences in demographic and clinical characteristics, such as BMI and marital status, were observed between the groups, suggesting a multifaceted risk profile for PE that includes genetic, environmental, and socio-economic factors. Conclusions: The study highlight the significant role of genetic variations, specifically the ACE G2350A (rs4343) polymorphism, in influencing PE predisposition. It highlights the intricate interplay between genetic predispositions and other risk factors in the development of PE. Further research is encouraged to expand on these findings and explore a wider range of genetic polymorphisms and their interactions with environmental factors.


Assuntos
Predisposição Genética para Doença , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/epidemiologia , Feminino , Gravidez , Estudos de Casos e Controles , Adulto , Fatores de Risco , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Fatores Socioeconômicos , Genótipo , Polimorfismo de Nucleotídeo Único
8.
Medicina (Kaunas) ; 60(6)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38929578

RESUMO

Background: Apolipoprotein E (APOE) gene polymorphism has been implicated in the pathogenesis of various metabolic disorders, including type 2 diabetes mellitus (T2DM). Type 2 diabetes mellitus (T2DM) is a major public health concern worldwide, including in Pakistan. Cardiovascular problems linked with T2DM have a significant impact on individuals and society. The goal of this study is to investigate the relationship between Apolipoprotein E (ApoE) genotypes, dyslipidemia, and cardiovascular complications such as ischemic heart disease (IHD) and stroke. Methods: This study was carried out on 260 subjects divided into controls and diabetics. The diabetics were further divided into four subgroups such as D1: diabetics without cardiovascular issues, D2: diabetics with heart disease, D3: diabetics with stroke, and D4: diabetics with both heart disease and stroke. Anthropometric parameters (age, BMI) and risk factors (smoking, diabetes duration, hypertension) were assessed in all groups. Serum levels of TC, TG, LDL, HDL, VLDL, creatinine, BSF, and HbA1c were also measured. Apolipoprotein E gene polymorphism was determined using PCR-RFLP. Results: Hypertension, BMI, and dyslipidemia are defined as elevated levels of total cholesterol, triglycerides, LDL, and VLDL, and decreased levels of HDL. Uncontrolled hyperglycemia (elevated fasting blood sugar and glycated hemoglobin) in T2DM was linked to vascular complications such as IHD and stroke. Hypertension was prevalent in 79.3% of the population. Stage 2 hypertension was more prevalent in all age groups. It was also noted that common genotypes in the Pakistani population are 3/3, 4/4, 2/3, and 3/4. The frequency of genotypes 3/4 and 2/3 is highest in diabetics with stroke. Genotype 3/3 is present frequently in diabetics with IHD/stroke and patients with both these complications. However, genotype 4/4 is most frequently found in diabetics with IHD. Conclusions: It is concluded that BMI, hypertension, hyperglycemia, atherosclerosis, and dyslipidemia are linked with cardiovascular complications of type 2 diabetes. Apolipoprotein E gene polymorphism is associated with cardiovascular disease in patients with diabetes by affecting the lipid profile.


Assuntos
Apolipoproteínas E , Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Paquistão/epidemiologia , Masculino , Feminino , Apolipoproteínas E/genética , Pessoa de Meia-Idade , Doenças Cardiovasculares/genética , Adulto , Polimorfismo Genético , Idoso , Fatores de Risco , Dislipidemias/genética , Dislipidemias/complicações , Genótipo , Acidente Vascular Cerebral/genética , Acidente Vascular Cerebral/complicações
9.
Nutrients ; 16(12)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38931158

RESUMO

Previous studies have reported that TT genotype carriers of the adenosine A2a receptor (ADORA2A) gene rs5751876 polymorphism have better ergogenic and anti-inflammatory responses to caffeine intake compared to C allele carriers. The aim of the present study was twofold: (1) to investigate the association of the ADORA2A rs5751876 polymorphism with acute caffeine supplementation on hormonal (growth hormone and testosterone) response to resistance exercise (RE); (2) to examine the relationship between the rs5751876 polymorphism and the resting levels of growth hormone and testosterone in athletes who are light caffeine consumers. A double-blind, crossover, placebo-controlled study involving 30 resistance-trained men (age 21.7 ± 4.1) was conducted to assess the impact of caffeine supplementation on serum growth hormone (GH) and testosterone (TS) levels before, immediately after, and 15 min post-RE. One hour before engaging in resistance exercise, subjects were randomly administered 6 mg of caffeine per kg of body mass or a placebo (maltodextrin). After a 7-day washout period, the same protocol was repeated. Resting testosterone and growth hormone levels were examined in the sera of 94 elite athletes (31 females, age 21.4 ± 2.8; 63 males, age 22.9 ± 3.8). Caffeine consumption led to significantly greater increases in GH and TS in men with the TT genotype compared to C allele carriers. Furthermore, in the group of athletes, carriers of the TT genotype had significantly higher testosterone (p = 0.0125) and growth hormone (p = 0.0365) levels compared to C allele carriers. In conclusion, the ADORA2A gene rs5751876 polymorphism may modify the effect of caffeine intake on the hormonal response to exercise.


Assuntos
Cafeína , Estudos Cross-Over , Suplementos Nutricionais , Receptor A2A de Adenosina , Treinamento Resistido , Testosterona , Humanos , Cafeína/administração & dosagem , Masculino , Método Duplo-Cego , Receptor A2A de Adenosina/genética , Adulto Jovem , Testosterona/sangue , Adulto , Feminino , Atletas , Polimorfismo de Nucleotídeo Único , Genótipo , Hormônio do Crescimento Humano/sangue , Polimorfismo Genético , Exercício Físico
10.
Viruses ; 16(6)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38932142

RESUMO

HIV-1 protease inhibitors are an essential component of antiretroviral therapy. However, drug resistance is a pervasive issue motivating a persistent search for novel therapies. Recent reports found that when protease activates within the host cell's cytosol, it facilitates the pyroptotic killing of infected cells. This has led to speculation that promoting protease activation, rather than inhibiting it, could help to eradicate infected cells and potentially cure HIV-1 infection. Here, we used a nanoscale flow cytometry-based assay to characterize protease resistance mutations and polymorphisms. We quantified protease activity, viral concentration, and premature protease activation and confirmed previous findings that major resistance mutations generally destabilize the protease structure. Intriguingly, we found evidence that common polymorphisms in the hinge domain of protease can influence its susceptibility to premature activation. This suggests that viral heterogeneity could pose a considerable challenge for therapeutic strategies aimed at inducing premature protease activation in the future.


Assuntos
Farmacorresistência Viral , Infecções por HIV , Protease de HIV , HIV-1 , Polimorfismo Genético , Protease de HIV/genética , Protease de HIV/metabolismo , HIV-1/genética , HIV-1/efeitos dos fármacos , HIV-1/enzimologia , Humanos , Farmacorresistência Viral/genética , Infecções por HIV/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Inibidores da Protease de HIV/farmacologia , Mutação
11.
Int J Mycobacteriol ; 13(2): 115-125, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38916380

RESUMO

The current meta-analysis aims to explore the potential correlation between natural resistance-associated macrophage protein 1 (NRAMP1) (3'-Untranslated region [3'-UTR]) and nucleotide-binding oligomerization domain-2 (NOD2 [rs8057341]) gene polymorphisms and their association with leprosy susceptibility in both Asian and Caucasian populations. Datas were retrieved from case control studies with NOD 2 and NRAMP 1 gene polymorphism associated with leprosy disease. Leprosy emerges as a particularly distinctive ailment among women on a global scale. The NRAMP1 (3'-UTR) and NOD2 (rs8057341) genetic variations play a crucial role in the progression of leprosy. A systematic review of relevant case-control studies was conducted across several databases, including ScienceDirect, PubMed, Google Scholar, and Embase. Utilizing MetaGenyo and Review Manager 5.4 Version, statistical analyses were carried out. Nine case-control studies totaling 3281 controls and 3062 leprosy patients are included in the research, with the objective of examining the potential association between NRAMP1 (3'-UTR) and NOD2 (rs8057341) gene polymorphisms and leprosy risk. The review methodology was registered in PROSPERO (ID520883). The findings reveal a robust association between NRAMP1 (3'-UTR) and NOD2 (rs8057341) gene polymorphisms and leprosy risk across various genetic models. Although the funnel plot analysis did not identify publication bias, bolstering these findings and elucidating potential gene-gene and gene-environment interactions require further comprehensive epidemiological research. This study identified a strong correlation between polymorphisms in the NOD2 (rs8057341) genes and susceptibility to leprosy across two genetic models. Further comprehensive epidemiological investigations are warranted to validate these findings and explore potential interactions between these genes and environmental factors.


Assuntos
Povo Asiático , Proteínas de Transporte de Cátions , Predisposição Genética para Doença , Hanseníase , Proteína Adaptadora de Sinalização NOD2 , População Branca , Humanos , Hanseníase/genética , Povo Asiático/genética , População Branca/genética , Proteínas de Transporte de Cátions/genética , Proteína Adaptadora de Sinalização NOD2/genética , Regiões 3' não Traduzidas/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Polimorfismo Genético , Masculino
12.
Int J Mol Sci ; 25(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38892458

RESUMO

Vitamin D-binding protein (DBP), also known as Gc-globulin, is a protein that affects several physiological processes, including the transport and regulation of vitamin D metabolites. Genetic polymorphisms in the DBP gene have a significant impact on vitamin D levels and may have implications for disease risk. DBP polymorphisms are linked to differential immune responses, which could influence the onset of juvenile diseases. This narrative review examines the various roles of DBP, with a focus on bone health, immunological regulation, and lipid metabolism in children. Chronic disorders affected by DBP polymorphisms include bone abnormalities, autoimmune diseases, cardiovascular issues, childhood asthma, allergies, cystic fibrosis, acute liver failure, celiac disease, inflammatory bowel disease, and chronic kidney disease. Future research should focus on identifying the processes that underpin the many roles that DBP plays and developing customized therapeutics to improve health outcomes in the juvenile population.


Assuntos
Proteína de Ligação a Vitamina D , Humanos , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo , Criança , Saúde da Criança , Vitamina D/metabolismo , Metabolismo dos Lipídeos , Polimorfismo Genético
13.
Nat Commun ; 15(1): 5333, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38909039

RESUMO

Balancing selection is an evolutionary process that maintains genetic polymorphisms at selected loci and strongly reduces the likelihood of allele fixation. When allelic polymorphisms that predate speciation events are maintained independently in the resulting lineages, a pattern of trans-species polymorphisms may occur. Trans-species polymorphisms have been identified for loci related to mating systems and the MHC, but they are generally rare. Trans-species polymorphisms in disease loci are believed to be a consequence of long-term host-parasite coevolution by balancing selection, the so-called Red Queen dynamics. Here we scan the genomes of three crustaceans with a divergence of over 15 million years and identify 11 genes containing identical-by-descent trans-species polymorphisms with the same polymorphisms in all three species. Four of these genes display molecular footprints of balancing selection and have a function related to immunity. Three of them are located in or close to loci involved in resistance to a virulent bacterial pathogen, Pasteuria, with which the Daphnia host is known to coevolve. This provides rare evidence of trans-species polymorphisms for loci known to be functionally relevant in interactions with a widespread and highly specific parasite. These findings support the theory that specific antagonistic coevolution is able to maintain genetic diversity over millions of years.


Assuntos
Daphnia , Polimorfismo Genético , Seleção Genética , Animais , Daphnia/genética , Daphnia/microbiologia , Daphnia/imunologia , Pasteuria/genética , Pasteuria/patogenicidade , Resistência à Doença/genética , Crustáceos/genética , Crustáceos/microbiologia , Crustáceos/imunologia , Evolução Molecular , Genoma/genética , Filogenia , Alelos
15.
Artigo em Inglês | MEDLINE | ID: mdl-38918943

RESUMO

INTRODUCTION: This study explores the immunogenetic associations of human leukocyte antigens (HLA) and the calcium release-activated calcium modulator 1 (ORAI1) and stromal interaction molecule 1 (STIM1) genes in HIV-1‒positive patients with HIV-related skin disorders. METHODS: This study assessed the distribution of variants of HLA class II alleles and expression levels of ORAI1 and STIM1 genes in the blood between HIV-1‒positive patients with HIV-related skin disorders and the control group with no HIV within the Latvian population. RESULTS: The research group comprised 115 HIV-1‒positive patients with HIV-related skin disorders, and the control group included 80 healthy individuals. Risk alleles (HLA- DQB1*02:01-0301 and HLA-DQA1*01:01-0501) and protective alleles (HLA-DRB1*07-13, DRB1*01-13, DRB1*04-11, and HLA-DQA1*05:01-0501) showed statistical significance in the groups. In 38 out of 115 patients, higher expression levels of ORAI1 and STIM1 genes were detected in the blood at the beginning of treatment. A significantly higher level of the microribonucleic acid (mRNA) ORAI1 gene was also found in the control group. CONCLUSIONS: The results demonstrate that HLA class II alleles are associated with a trend toward risk/protection concerning HIV-related skin disorders in HIV-1‒positive patients. It was also shown that a low level of ORAI1 mRNA and the risk allele HLA-DQB1*0201-0301 were simultaneously present in the research group.


Assuntos
Infecções por HIV , Proteína ORAI1 , Polimorfismo Genético , Molécula 1 de Interação Estromal , Humanos , Proteína ORAI1/genética , Masculino , Letônia , Feminino , Molécula 1 de Interação Estromal/genética , Adulto , Infecções por HIV/genética , Pessoa de Meia-Idade , Dermatopatias/genética , Estudos de Casos e Controles , Proteínas de Neoplasias/genética , Predisposição Genética para Doença
16.
PLoS One ; 19(6): e0305945, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38917122

RESUMO

Understanding the genetic diversity of existing genetic resources at the DNA level is an effective approach for germplasm conservation and utilization in breeding programs. However, the patterns of genetic diversity and population structure remain poorly characterized, making germplasm conservation and breeding efforts difficult to succeed. Thus, this study is aimed to evaluate the genetic diversity and population structure of 49 barley accessions collected from different geographic origins in Ethiopia. Twelve SSR markers were used to analyze all accessions and a total of 61 alleles were found, with a mean of 5.08 alleles per locus. The analysis pointed out the existence of moderate to high values of polymorphic information content ranging from 0.39 to 0.91 and the mean Shannon diversity index(I) was 1.25, indicating that they were highly informative markers. The highest Euclidean distance (1.32) was computed between accession 9950 and two accessions (247011 and 9949), while the lowest Euclidean distance (0.00) was estimated between accessions 243191 and 243192. The result of molecular variance analysis revealed that the highest variation was found among accessions (47) relative to within accessions (44) and among geographic origins (9). Cluster analysis grouped the 49 barley accessions into three major clusters regardless of their geographic origin which could be due to the presence of considerable gene flow (2.72). The result of the STRUCTURE analysis was consistent with neighbor-joining clustering and principal coordinate analysis. Generally, this study concluded that the variation among accessions was more important than the difference in geographical regions to develop an appropriate conservation strategy and for parental selection to use in breeding programs. This information will be helpful for barley conservation and breeding, and it may speed up the development of new competing barley varieties.


Assuntos
Variação Genética , Hordeum , Repetições de Microssatélites , Hordeum/genética , Etiópia , Repetições de Microssatélites/genética , Filogenia , Alelos , Marcadores Genéticos , Polimorfismo Genético , Análise por Conglomerados , Genética Populacional
17.
Sci Rep ; 14(1): 14688, 2024 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918489

RESUMO

In light of the multitude of olive trees cultivated and the lack of the genetic diversity of available genotypes to select varieties and lines that are characterized by high diversity and better performance under the corresponding conditions, A comparison analysis of the genotyping and morphological characteristics of eight olive cultivars growing in Saudi Arabia's Al-Jouf region was conducted and analyzed. Morpho-anatomical and chemical characteristics along with both inter-simple-sequence repeats (ISSRs) and start-codon-targeted (SCoT) markers were used to evaluate the genetic diversity among eight olive varieties in Al-Jouf, Saudi Arabia. Analyses of 27 morphological, chemical, and anatomical characteristics concluded the existence of genetic differences among the studied varieties. Moreover, six ISSR and eight SCoT primer combinations produced a total of 48 loci, of which 18 (10 ISSR and 8 SCoT) were polymorphic. The average polymorphism information content (PIC values of 0.48 and 0.44, respectively) and marker index (MI of 0.79 and 0.48, respectively) detected for ISSR and SCoT markers revealed the prevalence of high genetic diversity among the studied olive varieties. Based on chemical and anatomical characteristics and the selected molecular markers, the eight olive cultivars were grouped into two distinct clusters. Clusters in the adjacent joint dendrogram produced using ISSR, SCoT and combined data were similar, and grouped all individuals into two groups. However, the dendrogram generated on the basis of SCoT separated individuals into subgroups containing at least two varieties. The findings showed that both methods were effective in assessing diversity, and that SCoT markers can be used as a reliable and informative method for assessing genetic diversity and relationships among olive varieties and can serve as a complementary tool to provide a more complete understanding of the genetic diversity available in Olea europaea populations in Saudi Arabia.


Assuntos
Variação Genética , Repetições de Microssatélites , Olea , Olea/genética , Olea/classificação , Olea/anatomia & histologia , Arábia Saudita , Repetições de Microssatélites/genética , Genótipo , Polimorfismo Genético , Filogenia , Marcadores Genéticos
18.
Biol Pharm Bull ; 47(6): 1079-1086, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825461

RESUMO

Idiosyncratic drug toxicities (IDTs) pose a significant challenge; they are marked by life-threatening adverse reactions that emerge aftermarket release and are influenced by intricate genetic and environmental variations. Recent genome-wide association studies have highlighted a strong correlation between specific human leukocyte antigen (HLA) polymorphisms and IDT onset. This review provides an overview of current research on HLA-mediated drug toxicities. In the last six years, HLA-transgenic (Tg) mice have been instrumental in advancing our understanding of these underlying mechanisms, uncovering systemic immune reactions that replicate human drug-induced immune stimulation. Additionally, the potential role of immune tolerance in shaping individual differences in adverse effects highlights its relevance to the interplay between HLA polymorphisms and IDTs. Although HLA-Tg mice offer valuable insights into systemic immune reactions, further exploration is essential to decipher the intricate interactions that lead to organ-specific adverse effects, especially in organs such as the skin or liver. Navigating the intricate interplay of HLA, which may potentially trigger intracellular immune responses, this review emphasizes the need for a holistic approach that integrates findings from both animal models and molecular/cellular investigations. The overarching goal is to enhance our comprehensive understanding of HLA-mediated IDTs and identify factors shaping individual variations in drug reactions. This review aims to facilitate the development of strategies to prevent severe adverse effects, address existing knowledge gaps, and provide guidance for future research initiatives in the field of HLA-mediated IDTs.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Antígenos HLA , Animais , Humanos , Antígenos HLA/genética , Antígenos HLA/imunologia , Camundongos Transgênicos , Polimorfismo Genético , Camundongos
19.
BMC Plant Biol ; 24(1): 603, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926681

RESUMO

BACKGROUND: Chayote is a high economic crop in the Cucurbitaceae family, playing an important role in food production, disease treatment and the production of degradable materials in industries. Due to the harsh environment, such as high temperature, drought and frost, some chayote resources are gradually disappearing. It is crucial to collect, characterize, and conserve chayote resources. However, the genetic diversity of chayote resources in China has not been studied so far. RESULTS: In this study, we collected 35 individuals of chayote from 14 provinces in China. Subsequently, we found 363,156 SSR motifs from the chayote genome and designed 57 pairs of SSR primers for validation. Out of these, 48 primer pairs successfully amplified bands, with 42 of them showing polymorphism. These 42 primer pairs detected a total of 153 alleles, averaging 3.64 alleles per locus. The polymorphic information content ranged from 0.03 to 0.78, with an average value of 0.41, indicating a high level of polymorphism. Based on the analysis using STRUCTURE, PCoA, and UPGMA methods, the 35 chayote individuals were divided into two major clusters. Through further association analysis, 7 significantly associated SSR markers were identified, including four related to peel color and three related to spine. CONCLUSIONS: These molecular markers will contribute to the analysis of genetic diversity and genetic breeding improvement of chayote in the future.


Assuntos
Variação Genética , Genoma de Planta , Repetições de Microssatélites , Repetições de Microssatélites/genética , China , Marcadores Genéticos , Polimorfismo Genético
20.
Iran J Kidney Dis ; 18(3): 179-186, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38904338

RESUMO

INTRODUCTION: Diabetic nephropathy is one of the most common severe symptoms of diabetes mellitus. Hyperglycemia can lead to tissue damage and inflammation due to mediators such as receptor for advanced glycation end-products (RAGE). Therefore, in this study, we aimed to investigate the association between the G82S polymorphism of the RAGE gene and diabetic nephropathy in diabetic patients. METHODS: In this case-control study, 356 participants (158 men and 198 women) of Asian race, aged 45 to 65 years, who were diagnosed with type 2 diabetes mellitus based on their fasting plasma glucose levels were enrolled. DNA was isolated from the participants' blood samples and genotyped using TETRA -Primer ARMS-PCR. Serum protein concentration of soluble RAGE (sRAGE) was also determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Although we found differences in genotyping of participants between homozygous AA and GG and heterozygous GA in the studied groups, the differences were not significant (P = .568). In addition, we found no significant correlation between the G82S polymorphism of RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared with diabetic patients (P > .05). CONCLUSION: The results of this study indicate no significant association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. Serum levels of sRAGE were only slightly decreased in patients with diabetic nephropathy compared to diabetic patients without nephropathy. Therefore, the study suggests that there is probably no association between the G82S polymorphism in the gene RAGE and the development of diabetic nephropathy. DOI: 10.52547/ijkd.7872.


Assuntos
Povo Asiático , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Receptor para Produtos Finais de Glicação Avançada , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático/genética , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/sangue , Predisposição Genética para Doença , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Receptor para Produtos Finais de Glicação Avançada/genética , Receptor para Produtos Finais de Glicação Avançada/sangue
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