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1.
Anticancer Res ; 39(10): 5375-5380, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570432

RESUMO

BACKGROUND/AIM: Matrix metalloproteinases-11 (MMP-11) overexpression has been reported in various types of cancer including lung cancer. We aimed to examine the contribution of MMP-11 genotypes to lung cancer risk. MATERIALS AND METHODS: In this case-control study, the MMP-11 rs738791, rs2267029, rs738792 and rs28382575 genotypes were determined among 358 lung cancer patients and 716 age- and gender-matched healthy control Taiwanese. RESULTS: The percentages of rs738791 CT and TT were 50.6% and 9.2% in the case group, slightly higher than 48.5% and 8.1% in the control group (p for trend=0.5638). The allelic analysis showed that the rs738791 T allele did not confer lung cancer risk compared with the C allele. Similarly, there was no association between rs2267029, rs738792 or rs28382575 and lung cancer risk. There was no joint effect of MMP-11 genotypes among ever smokers or non-smokers. CONCLUSION: The genotypes of MMP-11 play a minor role in determining lung cancer risk in Taiwan.


Assuntos
Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Metaloproteinase 11 da Matriz/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taiwan
2.
Medicine (Baltimore) ; 98(38): e16991, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567936

RESUMO

BACKGROUND: Interleukin 12 (IL-12) and interleukin 12 receptor (IL12R), key inflammatory cytokines in the immune system, participate in bridging the innate immunity and adaptive immunity. No previous work has reported the role of IL-12 and IL12R in high-risk human papillomavirus (hrHPV) susceptibility. The purpose of this study was to investigate the association of IL-12, IL12R polymorphisms, and serum IL-12 levels with hrHPV susceptibility in rural women from Luohe, Henan, China. METHODS: Two hundred sixty cases with hrHPV infection and 260 healthy controls were selected. Enzyme-linked immunosorbent assays were used to detect the serum IL-12 levels, and the polymorphisms of IL12B rs3212227, IL12RB1 rs393548, and IL12RB1 rs436857 were determined using DNA sequencing. RESULTS: The serum IL-12 levels were significantly lower in cases with hrHPV infection compared with those in healthy controls (P < .01).There was no significant difference in IL12 rs3212227, IL12RB1rs436857, and IL12RB1rs393548 genotype and allele frequencies between cases and controls (P > .05). Furthermore, with respect to the IL12 rs3212227 polymorphism with serum IL-12 levels, although serum IL-12 levels were lower in cases than in controls, we did not find any differences between serum IL-12 levels and genotypes in cases(P > .05). CONCLUSIONS: Our data demonstrates that low serum IL-12 levels may be associated with hrHPV susceptibility but are not associated with IL-12 gene polymorphisms; furthermore, IL-12 and IL12R gene polymorphisms may not contribute susceptibility to hrHPV in rural women from Luohe, Henan, China.


Assuntos
Predisposição Genética para Doença , Subunidade p40 da Interleucina-12/genética , Infecções por Papillomavirus/genética , Receptores de Interleucina-12/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Subunidade p40 da Interleucina-12/sangue , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-12/sangue , População Rural
3.
Medicine (Baltimore) ; 98(38): e17224, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31567981

RESUMO

BACKGROUND: Multiple sclerosis (MS) is a common autoimmune disease of the central nervous system (CNS), and is associated with genetic factors. FOXP3 gene polymorphism has been reported as the risk factor for MS, however, previous studies have showed conflicting results. The purpose of this study is to investigate the association between FOXP3 gene polymorphism and the susceptibility to MS. METHODS: Pubmed, Embase, library of Cochrane, and Web of Science were used to search the eligible articles from January 1980 up to October 2018. The odds ratio (ORs) and its 95% confidence intervals (CI) were used to evaluate the strength of association. Allele model, homozygote model, heterozygote model, dominant model, and recessive model were used to evaluate the association between FOXP3 gene polymorphism and MS. RESULTS: A total of 5 studies contained 1276 MS patients and 1447 controls (for rs3761548) and 600 MS patients and 640 controls (for rs2232365) were enrolled in this meta-analysis. The association showed significant differences in allele and dominant model for rs3761548 polymorphism. In addition, a clear tendency to significance was detected in homozygote and recessive model for rs3761548 (P = .052). Subgroup analysis indicated a significant risk of MS in all genotype models but heterozygotes in Asians. CONCLUSION: FOXP3 gene polymorphism rs3761548 was associated with a higher MS risk, especially in Asians. This conclusion needs to be validated in more large samples and multiracial studies. LEVEL OF EVIDENCE: Level III diagnostic study.


Assuntos
Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença/genética , Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único/genética , Genes/genética , Humanos , Esclerose Múltipla/etiologia
4.
Anticancer Res ; 39(10): 5525-5530, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570446

RESUMO

BACKGROUND/AIM: Basal cell carcinoma (BCC) has been genetically associated with an increased expression of angiotensin-converting enzyme (ACE), an important factor of the renin-angiotensin system which produces vasoconstrictor angiotensin II. Other factors of this system include angiotensinogen (AGT) and angiotensin receptors AGTR1, AGTR2. We investigated the possible association of BCC with genetic variability in the AGT, AGTR1 and AGTR2 genes. MATERIALS AND METHODS: DNA samples of 190 Greeks were studied, including 91 patients with BCC and 99 matched healthy controls. Molecular genotyping of patients and controls was performed for the polymorphisms AGT M235T, AGTR1 A1166C and AGTR2 G1675A. RESULTS: The mutant T allele that increases AGT gene expression was detected in two-fold increased frequency in BCC patients in comparison to healthy controls (p <0.001). On the contrary, no significant difference was observed in AGTR1 and AGTR2 variants between patients and controls. CONCLUSION: Increased expression of AGT may be associated with BCC.


Assuntos
Carcinoma Basocelular/genética , Predisposição Genética para Doença/genética , Polimorfismo Genético/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinogênio/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 2 de Angiotensina/genética
5.
Med Clin North Am ; 103(6): 1055-1075, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31582004

RESUMO

This article presents a nongeneticist's guide to understanding the genetics of Parkinson disease (PD), including clinical diagnostic criteria, differential diagnoses, symptom management, when to suspect a hereditary factor, a summary of autosomal dominant and recessive PD genes, and proposed algorithm for genetic testing. There is increasing availability of genetic testing for PD but there are few recommendations on how these tests should be used in clinical practice. This article guides clinicians on the overall management of patients with PD, with emphasis on determining which patients should have genetic testing and how to interpret the results.


Assuntos
Testes Genéticos/métodos , Doença de Parkinson , Algoritmos , Gerenciamento Clínico , Predisposição Genética para Doença , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Doença de Parkinson/terapia
6.
Brain Nerve ; 71(10): 1039-1051, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588048

RESUMO

Dementia is a leading cause of death in many countries. Late-onset Alzheimer's disease (LOAD) is the most common form of dementia, with approximately 35 million affected people. LOAD shows a high heritability (h2) of 58-79%. Clarifying the genetic architecture of LOAD could contribute to precision medicine. In recent years, large-scale genome-wide association studies (GWASs) and their meta-analyses with a large sample size have elucidated the disease-susceptible genes and disease-causing pathways. To date, meta-analyses of GWASs in the Caucasian population have successfully identified approximately 40 LOAD risk loci. The gene set and disease pathway analysis obtained from the results of GWASs suggested biological mechanisms involving brain immune function, lipid-related processes, tau binding proteins, and degradation of amyloid precursor proteins in the pathogenesis of LOAD. Furthermore, the exome sequencing analysis in Japanese individuals with LOAD also revealed a rare variant with a large effect of SHARPIN in LOAD susceptibility, and the variant protein possibly affects the immune response through aberrant cellular localization, which may result in attenuated NF-κB activity in the brain. These findings could provide biological and pharmaceutical approaches in precision medicine for LOAD.


Assuntos
Doença de Alzheimer/genética , Patrimônio Genético , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença , Humanos , NF-kappa B/metabolismo , Ubiquitinas/genética , Proteínas tau/metabolismo
7.
Brain Nerve ; 71(10): 1071-1079, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588051

RESUMO

Next generation sequencing (NGS) technology has dramatically influenced the field of omics studies, such as genomics and transcriptomics. It is now possible to access a significant number of previously known and novel genomic variants through NGS. Although the effective manipulation and accurate interpretation of the inordinate amount of data may pose a considerable challenge, it enables us to identify specific genes responsible for causing or influencing the susceptibility to a plethora of diseases. Alzheimer's disease (AD) is the most common etiology of dementia in the elderly (approximately 60-70%). The current research trend of AD genetics focuses on the analysis of rare variants (allelic frequency <1%) instead of common variants (allelic frequency >1%) to identify AD-associated genes/variants. A number of genes (such as TREM2, ABCA7, SORL1) that carry rare pathogenic variants have reportedly conferred susceptibility to AD with stronger genetic risk effects (odds ratio >2.0). Here, we are going to introduce a small part of the latest many attractive findings about AD genetic researches.


Assuntos
Doença de Alzheimer/genética , Predisposição Genética para Doença , Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Frequência do Gene , Testes Genéticos , Genômica , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Glicoproteínas de Membrana/genética , Proteínas de Membrana Transportadoras/genética , Receptores Imunológicos/genética
8.
Brain Nerve ; 71(10): 1081-1088, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31588052

RESUMO

During the past 20 years, genome studies for Alzheimer's disease (AD) have elucidated the pathogenesis of AD including the amyloid hypothesis. However, clinical trials of the disease modifying drugs for AD developed based on the amyloid hypothesis have been largely unsuccessful. New genes associated with AD have been identified through comprehensive genome analyses such as genome-wide association studies and whole genome/exome sequencing using next-generation sequencers. With these efforts, new therapeutic targets to AD have been explored. This review summarizes the genetic make-up of AD in terms of both risk and protective factors from the viewpoint of novel therapeutic targets to AD.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/terapia , Testes Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fatores de Proteção , Fatores de Risco
9.
Exp Suppl ; 111: 149-169, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588532

RESUMO

Adrenocortical malignancies can occur in the context of several tumor predisposition syndromes.The Carney complex (CNC) is responsible for the majority of primary pigmented nodular adrenal diseases and is more rarely associated with adrenocortical carcinoma (ACC). Other core manifestations of CNC include cardiac and cutaneous myxomas, lentiginosis, somatotroph pituitary adenomas, Sertoli tumors, melanocytic schwannoma, and thyroid, breast, and bone tumors. CNC is mostly due to germline inactivating mutations of PRKAR1A.The majority of childhood ACC are related to genetic predisposition. The Beckwith-Wiedemann syndrome (BWS) is an overgrowth and tumor predisposition syndrome due to genetic or epigenetic alterations at the 11p15 locus. Classical tumor spectrum of BWS includes embryonal tumors and childhood ACC. The Li-Fraumeni syndrome (LFS) is a devastating tumor predisposition syndrome, due to germline inactivating mutations of TP53, and characterized by a high, various, and early-onset cancer risk. LFS spectrum includes premenopausal breast cancer, soft-tissue sarcoma, osteosarcoma, central nervous system tumor, and ACC, accounting for 50-80% of pediatric cases. Finally, germline predisposition affects up to 10% of adult ACC patients, mostly in part of LFS and Lynch syndrome.This chapter focuses on the diagnosis, screening, and management of adrenal tumors in part of these tumor predisposition syndromes.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Carcinoma Adrenocortical/genética , Síndrome de Beckwith-Wiedemann/genética , Complexo de Carney/genética , Síndrome de Li-Fraumeni/genética , Predisposição Genética para Doença , Humanos
10.
Forensic Sci Int Genet. ; 42: 203-212, Sept., 2019. tab.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1022691

RESUMO

ABSTRACT: Drug-induced arrhythmia is an adverse drug reaction that can be potentially fatal since it is mostly related to drug-induced QT prolongation, a known risk factor for Torsade de Pointes and sudden cardiac death (SCD). Several risk factors have been described in association to these drug-induced events, such as preexistent cardiac disease and genetic variation. Our objective was to study the genetic susceptibility in pharmacodynamic and pharmacokinetic pathways underlying suspected drug-induced arrhythmias and sudden unexplained deaths in 32 patients. The genetic component in the pharmacodynamic pathway was studied by analysing 96 genes associated with higher risk of SCD through massive parallel sequencing. Pharmacokinetic-mediated genetic susceptibility was investigated by studying the genes encoding cytochrome P450 enzymes using mediumthroughput genotyping. Pharmacodynamic analysis showed three probably pathogenic variants and 45 variants of uncertain significance in 28 patients, several of them previously described in relation to mild or late onset cardiomyopathies. These results suggest that genetic variants in cardiomyopathy genes, in addition to those related with channelopathies, could be relevant to drug-induced cardiotoxicity and contribute to the arrhythmogenic phenotype. Pharmacokinetic analysis showed three patients that could have an altered metabolism of the drugs they received involving CYP2C19 and/or CYP2D6, probably contributing to the arrhythmogenic phenotype. The study of genetic variants in both pharmacodynamic and pharmacokinetic pathways may be a useful strategy to understand the multifactorial mechanism of drug-induced events in both clinical practice and forensic field. However, it is necessary to comprehensively study and evaluate the contribution of the genetic susceptibility to drug-induced cardiotoxicity. (AU)


Assuntos
Farmacocinética , Predisposição Genética para Doença
11.
Zhonghua Liu Xing Bing Xue Za Zhi ; 40(8): 997-1002, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31484268

RESUMO

Objective: To explore the association between preeclampsia/eclampsia and maternal and fetal angiotensinogen SNPs. Methods: From January 2008 to October 2015, a case-parents/mother-control designed study was conducted among 347 preeclampsia/eclampsia cases and 700 controls to collect related information on their demographic characteristics and to detect the related angiotensinogen SNPs' genotypes. Both log-linear and unconditional logistic regression methods were employed to investigate the genetic effects of maternal/fetal angiotensinogen SNPs on preeclampsia/eclampsia. Multivariate binary unconditional logistic regression model and covariance were used to analyze the relationship between BMI before pregnancy, weight gain during pregnancy and overweight and obesity in preschool children. Results: Both fetal angiotensinogen rs3789679 GA and AA genotype were associated with the reduced risks of preeclampsia/eclampsia, with ORs as 0.73 (95%CI: 0.55-0.96) and 0.62 (95%CI: 0.39-0.98), respectively. For fetal angiotensinogen rs2493132, individuals that carrying the TT genotype, presented a positive association with the risk of preeclampsia/eclampsia, with OR as 1.60 (95%CI: 1.08-2.37). However, these associations were not statistically significant after the correction of the false discovery rate. It was observed that fetal rs3789679 could reduce the risk of preeclampsia/eclampsia (OR=0.73, 95%CI: 0.55-0.96) under the dominant model (GA+AA/GG) while fetal rs2493132 increased the risk of preeclampsia/eclampsia (OR=1.66, 95%CI: 1.13-2.44) under the recessive model (TT/CC+CT). Maternal rs5051 presented an association with preeclampsia/eclampsia (OR=1.33, 95%CI: 1.01-1.76) under the dominant model (TC+CC/TT). Conclusions: Results from the dominant model showed that both fetal rs3789679 GA and AA genotype reduced the risk of preeclampsia/eclampsia and maternal rs5051 TC while CC genotype increased the risk of preeclampsia/eclampsia. Fetal rs2493132 TT genotype seemed to be associated with the risk of preeclampsia/eclampsia under the recessive model.


Assuntos
Angiotensinogênio/genética , Eclampsia/genética , Polimorfismo de Nucleotídeo Único/genética , Pré-Eclâmpsia/genética , Angiotensinogênio/sangue , Estudos de Casos e Controles , Eclampsia/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Pré-Eclâmpsia/sangue , Gravidez , Cuidado Pré-Natal
12.
Tumour Biol ; 41(9): 1010428319872092, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31486713

RESUMO

Angiogenesis, induced by the vascular endothelial growth factor A through its ligation to the vascular endothelial growth receptor 2, has been described as a crucial point in high-grade glioma development. The aim of this study was to evaluate the influence of VEGFA-2578C/A, -2489C/T, -1154G/A, -634G/C, and -460C/T, and KDR-604T/C, -271G/A, +1192G/A, and +1719A/T single-nucleotide polymorphisms on risk and clinicopathological aspects of high-grade glioma. This case-control study enrolled 205 high-grade glioma patients and 205 controls. Individuals with VEGFA-2578 CC or CA, VEGFA-1154 GG, VEGFA-634 GC or CC, and VEGFA-460 CT or TT genotypes were under 2.56, 1.53, 1.54, and 1.84 increased risks of high-grade glioma, compared to others, respectively. And 1.61, 2.66, 2.52, 2.53, and 2.02 increased risks of high-grade glioma were seen in individuals with VEGFA-2578 CC plus VEGFA-1154 GG, VEGFA-2578 CC or CA plus VEGFA-634 GC or CC, VEGFA-2578 CC or CA plus VEGFA-460 CT or TT, VEGFA-1154 GG or GA plus VEGFA-634 GC or CC, and VEGFA 634 GC or CC plus VEGFA-460 CT or TT combined genotypes, respectively, when compared to others. The "CAGT" haplotype of KDR single-nucleotide polymorphisms was more common in patients with grade IV than in those with grade III tumors, and individuals carrying this haplotype were at 1.76 increased risk of developing grade IV tumors than others. We present, for the first time, preliminary evidence that VEGFA-2578C/A and VEGFA-1154G/A single-nucleotide polymorphisms increases high-grade glioma risk, and "CAGT" haplotype of the KDR gene alters high-grade glioma aggressiveness and risk of grade IV tumors in Brazil.


Assuntos
Glioma/genética , Haplótipos , Polimorfismo de Nucleotídeo Único , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Fatores de Risco , Adulto Jovem
13.
Pol J Pathol ; 70(2): 127-133, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31556563

RESUMO

We tested the association between HOXB13 G84E (rs138213197) germline mutation and PC risk in Polish men. DNA from 103 consecutive, newly diagnosed patients hospitalised because of PC and DNA from 103 men: volunteers, healthy at the time of the study. The G84E mutation was genotyped using Sanger sequencing. The HOXB13 G84E germline mutation was detected in 2.9% of PC men (3/103) and not detected in any healthy man. Two mutation carriers originated from two of 25 families fulfilling hereditary prostate cancer criteria (HPC) and one mutation carrier from one family among 78 families without HPC (PC frequency: 8% vs. 1.3%, OR = 6.70, p = 0.13). In two of three mutation carriers, disease was detected above 60 years of age. There was a trend for a lower probability of 5-year survival in patients with G84E than in patients without it (66.7% vs. 94.0%, p = 0.08). The HOXB13 G84E germline mutation is associated with increased prostate cancer risk in Polish men, with hereditary form of the disease, and probably with older age at PC onset (> 60 years of age) and shorter survival. However, it is not associated with PSA level, or PC stage or grade at the time of diagnosis.


Assuntos
Mutação em Linhagem Germinativa , Proteínas de Homeodomínio/genética , Neoplasias da Próstata/genética , Idoso , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Polônia , Antígeno Prostático Específico/sangue , Fatores de Risco
14.
J Assoc Physicians India ; 67(7): 43-48, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31559768

RESUMO

Aim: To delineate the genetic differences in polymorphism of the APOE and D2S439 marker genes for patients with and without rheumatoid arthritis and to study the distribution frequency of the prevalent alleles of these genes in clinically defined sub groups of patients/controls of Indian origin, specifically and their correlation with severity of disease using DAS score. Material and Methods: This is a case control study where peripheral blood samples 160 cases and 150 controls were collected. Results: We evaluated the association of the tetra nucleotide repeat microsatellite marker D2S439 lying at 231.27cM position on the q arm of chromosome-2. The alleles of this marker ranged in size from 163bp-203bp in PCR product length corresponding to 5-15 (CTAT)n tetra repeats. The allele frequencies for this marker in the North Indian population are different from the CEPH populations. The longer alleles, >199bp (=14 or 15 CTAT repeats) were not observed. The genotypes after bimodal distribution differ significantly among cases and controls (p=0.003). Statistically significant difference was seen between cases and controls for ≥(CTAT) 10 longer allele which was more prevalent in the adult RA cases than in controls. Severity of RA was defined by a DAS28 score of >6 on a scale of ten. No significant association was seen with the APOE polymorphism and disease severity. Conclusion: The long allele of D2S439 marker representing an expansion of the CTAT, tetranucleotide repeat doubles an individual's the risk for developing RA.


Assuntos
Apolipoproteínas E/genética , Artrite Reumatoide , Repetições de Microssatélites , Adulto , Estudos de Casos e Controles , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Índice de Gravidade de Doença
15.
An Acad Bras Cienc ; 91(3): e20180882, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31553368

RESUMO

Fragile X Syndrome (FXS) is a neurodevelopmental disorder caused by dynamic mutations of a CGG repetition segment in an X chromosome's single gene. It is considered the leading hereditary cause of both Autism Spectrum Disorders and Intellectual Disability. Some authors suggest that all individuals diagnosed with some of these latter conditions to be clinically and molecularly trialled for FXS due to the high levels of comorbidity between both conditions and also due to the variable expressiveness of this syndrome. This study has focused on verifying the presence of FMR1 expanded alleles since there is a lack of information about this kind of mutation in autism patients from the northern region of Brazil. The presence of large alleles for this gene could offer new therapeutic or pharmacological methods for the treatment of these patients. Both the presence and the frequency of CGG expansions were verified in 90 autism males by molecular analysis. Four of them had intermediate alleles and four others presented premutated alleles. Premutation carriers are on the propensity of developing the late onset Fragile X-associated tremor/ataxia syndrome. No full mutation alleles were found. Further studies are necessary to obtain more accurate statistical data about this kind of dynamic mutation.


Assuntos
Transtorno do Espectro Autista/genética , Proteína do X Frágil de Retardo Mental/genética , Síndrome do Cromossomo X Frágil/genética , Mutação/genética , Adolescente , Alelos , Criança , Pré-Escolar , Predisposição Genética para Doença , Testes Genéticos , Humanos , Masculino , Adulto Jovem
16.
Isr Med Assoc J ; 21(7): 487-490, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507126

RESUMO

BACKGROUND: Recurrent pericarditis is a state of repetitive inflammation of the pericardium with intervals of remission. The etiology of recurrent pericarditis is still largely unknown, yet most causes are presumed to be immune mediated. Genetic factors, including human leukocyte antigen (HLA) haplotypes, can be involved in dysregulation of the immune system and as a predisposition to several autoimmune conditions, including recurrent pericarditis. Several diseases are frequently associated with such manifestations. They include systemic lupus erythematosus, familial Mediterranean fever, and tumor necrosis factor receptor-associated periodic syndrome. However, idiopathic recurrent pericarditis remains the most frequently observed clinical condition and the conundrum of this disease still needs to be solved.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Pericardite/fisiopatologia , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/imunologia , Antígenos HLA/genética , Haplótipos , Humanos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/imunologia , Pericardite/genética , Pericardite/imunologia , Recidiva
17.
Anticancer Res ; 39(9): 4767-4773, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519577

RESUMO

BACKGROUND/AIM: Rs3824129 is a functional six-nucleotide insertion(I)/deletion(D) polymorphism in the promoter region of caspase 8, an essential apoptosis gene. We aimed to examine the association of this polymorphism with the risk of bladder cancer in the Taiwanese population. MATERIALS AND METHODS: Caspase-8 rs3834129 genotypes were determined and their associations with bladder cancer risk were evaluated among 375 patients and 375 controls by the PCR-RFLP methodology. In addition, the interaction of caspase-8 rs3834129 genotypes with personal behaviors and clinicopathological features were examined. RESULTS: The frequencies of II, ID and DD genotypes for caspase-8 rs3834129 were non-differentially distributed between the two groups (p for trend=0.7187). Analysis of allelic frequency distribution also indicated that the D variant allele was not associated with a risk of bladder cancer. There was no obvious joint interaction between caspase-8 rs3834129 genotypes and smoking, alcohol consumption, and clinical stage and grade. CONCLUSION: Caspase-8 rs3834129 genotypes play a minor role in the personal susceptibility to bladder cancer in Taiwan.


Assuntos
Caspase 8/genética , Predisposição Genética para Doença , Genótipo , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Taiwan , Neoplasias da Bexiga Urinária/patologia
18.
Anticancer Res ; 39(9): 4933-4940, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519598

RESUMO

BACKGROUND: Interleukin 2 (IL2) is a significant factor activating T-cell-mediated immune response by stimulation of natural killer cells, T-cells and in development of regulatory T (Treg) cells. Recent studies have that IL2 participates in cancer development by modifying the local immune response. Based on the suggested role of the single nucleotide polymorphisms (SNPs) rs2069762, rs6822844 and rs11938795 of IL2 in the pathogenesis of certain diseases, the relationship of these SNPs with clinicopathological variables and their possible implication for prognosis and disease outcome were evaluated in a cohort of Swedish patients with colorectal cancer (CRC). MATERIALS AND METHODS: TaqMan SNP genotype assays based on polymerase chain reaction were used for analysis of the IL2 SNPs in 467 patients with CRC and 467 healthy controls. Expression analysis of IL2 in plasma and CRC tissue was also performed. RESULTS: The allelic variants T in rs11938795 and G in rs6822844 were significantly associated with a higher risk of CRC. Kaplan-Meier analysis showed that cancer-specific survival was worse for individuals with C allele for rs2069762 with stage II CRC and with T allele for rs6822844 with stage III CRC. CONCLUSION: SNPs rs2069762, rs6822844 and rs11938795 of the IL2 gene may be helpful as prognostic biomarkers in the follow-up and management of the patients.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Variação Genética , Interleucina-2/genética , Adulto , Idoso , Alelos , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/imunologia , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Imunomodulação , Interleucina-2/sangue , Interleucina-2/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Prognóstico , Medição de Risco
19.
Hum Genet ; 138(10): 1183-1200, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471722

RESUMO

The glutamate pyruvate transaminase 2 (GPT2) gene produces a nuclear-encoded mitochondrial enzyme that catalyzes the reversible transfer of an amino group from glutamate to pyruvate, generating alanine and alpha-ketoglutarate. Recessive mutations in GPT2 have been recently identified in a new syndrome involving intellectual and developmental disability (IDD), postnatal microcephaly, and spastic paraplegia. We have identified additional families with recessive GPT2 mutations and expanded the phenotype to include small stature. GPT2 loss-of-function mutations were identified in four families, nine patients total, including: a homozygous mutation in one child [c.775T>C (p.C259R)]; compound heterozygous mutations in two siblings [c.812A>C (p.N271T)/c.1432_1433delGT (p.V478Rfs*73)]; a novel homozygous, putative splicing mutation [c.1035C>T (p.G345=)]; and finally, a recurrent mutation, previously identified in a distinct family [c.1210C>T (p.R404*)]. All patients were diagnosed with IDD. A majority of patients had remarkably small stature throughout development, many < 1st percentile for height and weight. Given the potential biological function of GPT2 in cellular growth, this phenotype is strongly suggestive of a newly identified clinical susceptibility. Further, homozygous GPT2 mutations manifested in at least 2 of 176 families with IDD (approximately 1.1%) in a Pakistani cohort, thereby representing a relatively common cause of recessive IDD in this population, with recurrence of the p.R404* mutation in this population. Based on variants in the ExAC database, we estimated that approximately 1 in 248 individuals are carriers of moderately or severely deleterious variants in GPT2.


Assuntos
Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/genética , Genes Recessivos , Predisposição Genética para Doença , Mutação , Fenótipo , Transaminases/genética , Adolescente , Alelos , Substituição de Aminoácidos , Deficiências do Desenvolvimento/metabolismo , Ativação Enzimática , Éxons , Feminino , Frequência do Gene , Estudos de Associação Genética , Genética Populacional , Genótipo , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Imagem por Ressonância Magnética , Masculino , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Moleculares , Linhagem , Conformação Proteica , Sítios de Splice de RNA , Análise de Sequência de DNA , Relação Estrutura-Atividade , Transaminases/química , Transaminases/metabolismo
20.
Medicine (Baltimore) ; 98(37): e17136, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517853

RESUMO

BACKGROUND: DRD2 TaqIA polymorphism may be associated with an increased risk of developing Parkinson disease (PD). However, the individual study's results are still inconsistent. METHODS: A meta-analysis of 4232 cases and 4774 controls from 14 separate studies were performed to explore the possible relationship between the DRD2 TaqIA gene polymorphism and PD. Pooled odds ratios (ORs) for the association and the corresponding 95% confidence intervals (CIs) were evaluated by a fixed-effect model. RESULTS: The pooled results revealed a significant association between DRD2 gene TaqIA polymorphism under recessive genetic model (OR: 0.91, 95% CI:0.83,0.99, P = .031) and additive genetic models (OR:0.93,95%CI:0.87,0.99, P = .032), but not associated with PD susceptibility under other genetic models in the whole population. Moreover, subgroups based on ethnicity and genotyping methods showed this association in the Caucasian subgroup under recessive genetic model (OR: 0.85, 95% CI:0.76,0.95, P = .003) and additive genetic models (OR:0.87,95%CI:0.79,0.96, P = .004) were existed. Besides, no significant association was detected under 6 genetic models in the Asian populations and PCR-RFLP subgroup. CONCLUSIONS: The current meta-analysis suggested that a significant association between DRD2 TaqIA polymorphism and PD under the recessive genetic mode, and additive genetic models, especially in Caucasians.


Assuntos
Predisposição Genética para Doença , Doença de Parkinson/genética , Polimorfismo Genético , Receptores de Dopamina D2/genética , Humanos , Doença de Parkinson/etnologia
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