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1.
Gene ; 723: 144133, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31589956

RESUMO

BACKGROUND AND AIM: Autism spectrum disorder (ASD) is one of the neurodevelopmental and cognitive conditions that involves 1 in 160 children around the world. Several studies showed that there is a relationship between vitamin D receptor (VDR) gene polymorphisms with the neurodevelopmental behavioral disorders. In the current study, we aimed to highlight the association of VDR gene polymorphisms (FokI and TaqI) with the risk of autism in Birjand population. MATERIAL AND METHODS: In this case-control study eighty-one patients recognized with ASD and one hundred-eight healthy controls were recruited to the study from 2017 to 2018. Genotyping was carried out by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) technique for all subjects. RESULTS: Calculated odds ratio and P-value for the alleles of VDR gene FokI and TaqI variants between autistic patients and controls did not show a significant difference (P > 0.05). However, calculated homozygous recessive (tt) for TaqI polymorphism was statistically significant (P = 0.015) in control group and there was also statistically meaningful difference in both case and control groups in ft haplotype (P = 0.04). CONCLUSION: These results provide preliminary evidence that genetic variants of the VDR gene (FokI and TaqI) might have a possible reduced risk of ASD occurrence in children. The additional examination is needed to acquire more decisive and precise results in this area.


Assuntos
Transtorno do Espectro Autista/genética , Polimorfismo de Fragmento de Restrição , Receptores de Calcitriol/genética , Adolescente , Transtorno do Espectro Autista/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Colecalciferol/sangue , Feminino , Estudos de Associação Genética , Testes Genéticos , Humanos , Irã (Geográfico) , Masculino
2.
BMC Genomics ; 20(1): 771, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31646968

RESUMO

BACKGROUND: The important property of the quantitative traits of model organisms is time-dependent. However, the methodology for investigating the genetic interaction network over time is still lacking. Our study aims to provide insights into the mechanistic basis of epistatic interactions affecting the phenotypes of model organisms. RESULTS: We performed an exhaustive genome-wide search for significant SNP-SNP interactions associated with male birds' body weight (BW) (n = 475) at multiple time points (day of hatch (BW0) and 1, 3, 5, and 7 weeks (BW1, BW3, BW5, and BW7)). Statistical analysis detected 67, four, and two significant SNP pairs associated with BW0, BW1, and BW3, respectively, with a significance threshold at 8.67 × 10- 12 (Bonferroni-adjusted: 1%). Meanwhile, no significant SNP pairs associated with BW5 and BW7 were found. The SNP-SNP interaction networks of BW0, BW1, and BW3 were built and annotated. CONCLUSIONS: With strong annotated information and a strict significant threshold, SNP-SNP interactions underpinned the gene-gene interactions that might occur between chromosomes or within the same chromosome. Comparing and combing the networks, the results indicated that the genetic network for chicken body weight was dynamic and time-dependent.


Assuntos
Peso Corporal/genética , Galinhas/genética , Epistasia Genética , Polimorfismo de Nucleotídeo Único , Animais , Estudos de Associação Genética , Masculino , Fenótipo
3.
An Bras Dermatol ; 94(4): 429-433, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644615

RESUMO

BACKGROUND: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. OBJECTIVE: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. METHODS: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. RESULTS: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. STUDY LIMITATIONS: Lack of studies on various racial or ethnic groups and small sample size. CONCLUSION: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.


Assuntos
Síndrome de Behçet/genética , Receptor Celular 2 do Vírus da Hepatite A/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Humanos , Irã (Geográfico) , Modelos Logísticos , Masculino , Reação em Cadeia da Polimerase Multiplex , Medição de Risco , Fatores de Risco
4.
Medicine (Baltimore) ; 98(40): e17414, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577754

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are small noncoding single-stranded RNAs with a length of ∼21 nucleotides. Single nucleotide polymorphisms (SNPs) may affect the function of miRNAs, resulting in a variety of disorders in vivo. Recently, diabetes mellitus (DM) has become a global healthcare problem, and several studies have reported that 2 common polymorphisms (miRNA 146a rs2910164 and miRNA 27a rs895819) are related to susceptibility to diabetes. Given that no consensus had been reached regarding the association of the 2 polymorphisms with diabetes, we conducted this meta-analysis. METHODS: Four databases (PubMed, EMBASE, Cochrane, and Web of Science) were searched up to January 9, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association strength. Subgroup and sensitivity analyses were also performed. RESULTS: Six studies involving 2585 cases and 2435 controls for miR146a rs2910164 and 5 studies involving 2922 cases and 2781 controls for miR27a rs895819 were ultimately analyzed in our meta-analysis. Based on pooled results, no statistical significance in association between rs2910164 and diabetes in Caucasians, Asians, or type 2 diabetes was observed in any genetic models. Nevertheless, we found a significant correlation between miRNA27a rs895819 and diabetes in the homozygote model (CC vs TT: OR = 0.58, 95%CI [0.35,0.98]) and recessive model (CC vs CT + TT: OR = 0.59, 95%CI [0.36,0.97]). By performing subgroup analysis, we also observed that C allele conveyed a significant protective effect against diabetes development in Caucasians (C vs T: OR = 0.67, 95%CI [0.52,0.85]). CONCLUSION: In conclusion, this meta-analysis indicated that miRNA27a rs895819 might play a protective role in diabetes, and miRNA146a rs2910164 likely had no association with diabetes.


Assuntos
Diabetes Mellitus/genética , MicroRNAs/genética , Grupo com Ancestrais do Continente Asiático , Diabetes Mellitus Tipo 2/genética , Grupo com Ancestrais do Continente Europeu , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Fatores de Risco
5.
Int Braz J Urol ; 45(5): 901-909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31626518

RESUMO

PURPOSE: It has been reported that calcitonin receptor (CALCR) gene polymorphisms might be associated with calcium stone urolithiasis. Owing to mixed and inconclusive results, we conducted a meta-analysis to summarize and clarify this association. MATERIALS AND METHODS: A systematic search of studies on the association between CALCR gene polymorphisms and calcium stone urolithiasis susceptibility was conducted in databases. RESULTS: Odds ratios and 95% confi dence intervals were used to pool the effect size. Five articles were included in our meta-analysis. CONCLUSIONS: CALCR rs1801197 might be associated with increased risk of calcium stone urolithiasis. There is insufficient data to fully confirm the association between CALCR rs1042138 and calcium stone urolithiasis susceptibility. Well-designed studies with larger sample size and more subgroups are required to validate the risk identified in the current meta-analysis.


Assuntos
Polimorfismo de Nucleotídeo Único , Receptores da Calcitonina/genética , Urolitíase/genética , Cálcio/metabolismo , Feminino , Estudos de Associação Genética , Humanos , Masculino , Medição de Risco , Fatores de Risco
6.
Arch Virol ; 164(12): 2909-2918, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31520221

RESUMO

CYP27A1, CYP2R1 and CYP27B1 hydroxylases are involved in the synthesis of 1, 25-hydroxyvitamin D3, which plays a role in the immune regulation and pathogenesis of hepatitis C virus (HCV) infection. The aim of the present study was to investigate the relationships between polymorphisms in vitamin D pathway genes and HCV infection outcomes in a Chinese population. Nine single-nucleotide polymorphisms (SNPs) of CYP27A1, CYP2R1 and CYP27B1 were genotyped in a high-risk Chinese population. The distributions of these SNPs were compared among groups with different outcomes of HCV infection, including 863 cases of persistent HCV infection, 524 cases of spontaneous clearance, and 1079 uninfected controls. The results showed that the CYP2R1 rs12794714-G, rs10741657-A, rs1562902-C, and rs10766197-G alleles were significantly associated with increased susceptibility to HCV infection (all PFDR < 0.05, in additive/dominant models), and the combined effect of the four unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 0.008). Moreover, haplotype analysis suggested that, compared with the most frequent haplotype (Ars12794714Grs10741657Trs1562902Ars10766197), the haplotype containing four unfavorable alleles, GACG, was associated with a higher risk of HCV infection. The results of our study suggest that genetic variants in CYP2R1 may be biomarkers for predicting the susceptibility to HCV infection in the Chinese population.


Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , Colestanotriol 26-Mono-Oxigenase/genética , Família 2 do Citocromo P450/genética , Hepatite C/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Hepatite C/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Vitamina D/metabolismo
7.
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
8.
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
9.
DNA Cell Biol ; 38(10): 1155-1165, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31433201

RESUMO

Our previous genome-wide association study has identified a suggestive association at rs11264799 within FCRL3 (Fc receptor-like 3) locus on 1q23.1 for IgA nephropathy (IgAN) in a Chinese Han population. This study aims to investigate the association of FCRL3 variants with the susceptibility, clinicopathological phenotypes and prognosis of IgAN. Eleven FCRL3 single-nucleotide polymorphisms (SNPs) were selected and analyzed in this two-stage case/control study with a total of 1750 IgAN cases and 2500 healthy controls in a Chinese Han population. Unconditional logistic regression models were used to estimate odds ratios and 95% confidence intervals (CIs) as implemented in the PLINK software. Luciferase assays were applied to detect the allelic effect of rs11264794 on gene expression regulation. We found that four SNPs (rs11264794, rs7865684, rs11264799, and rs6691569) were significantly associated with IgAN susceptibility after Bonferroni correction in the combined samples. Genotype/phenotype association analysis observed that two SNPs (rs11264794 and rs11264793) were associated with less disease severity. After adjusting for confounders, rs11264794 was independently correlated with renal outcome in IgAN patients (hazard ratio = 0.64, 95% CI = 0.43-0.97, p = 0.033). In addition, the protective allele A of rs11264794 was significantly associated with higher FCRL3 gene expression. Furthermore, luciferase reporter gene assays demonstrated that the minor allele of rs11264794 obviously reduced the specific binding between miR-183-5p.1 and FCRL3 3'-untranslated region. Our results indicate that FCRL3 gene polymorphisms are associated with the development and progression of IgAN, and the rs11264794-A allele showed a protective role for IgAN.


Assuntos
Predisposição Genética para Doença , Glomerulonefrite por IGA/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Receptores Imunológicos/genética , Regiões 3' não Traduzidas , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Expressão Gênica , Genes Reporter , Estudos de Associação Genética , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/etnologia , Glomerulonefrite por IGA/patologia , Humanos , Modelos Logísticos , Luciferases/genética , Luciferases/metabolismo , Masculino , MicroRNAs/metabolismo , Razão de Chances , Fenótipo , Prognóstico , Receptores Imunológicos/metabolismo , Índice de Gravidade de Doença
10.
Hum Genet ; 138(10): 1171-1182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31367973

RESUMO

Age-related macular degeneration (AMD) is a leading cause of blindness in the world. While dozens of independent genomic variants are associated with AMD, about one-third of AMD heritability is still unexplained. To identify novel variants and loci for AMD, we analyzed Illumina HumanExome chip data from 87 Amish individuals with early or late AMD, 79 unaffected Amish individuals, and 15 related Amish individuals with unknown AMD affection status. We retained 37,428 polymorphic autosomal variants across 175 samples for association and linkage analyses. After correcting for multiple testing (n = 37,428), we identified four variants significantly associated with AMD: rs200437673 (LCN9, p = 1.50 × 10-11), rs151214675 (RTEL1, p = 3.18 × 10-8), rs140250387 (DLGAP1, p = 4.49 × 10-7), and rs115333865 (CGRRF1, p = 1.05 × 10-6). These variants have not been previously associated with AMD and are not in linkage disequilibrium with the 52 known AMD-associated variants reported by the International AMD Genomics Consortium based on physical distance. Genome-wide significant linkage peaks were observed on chromosomes 8q21.11-q21.13 (maximum recessive HLOD = 4.03) and 18q21.2-21.32 (maximum dominant HLOD = 3.87; maximum recessive HLOD = 4.27). These loci do not overlap with loci previously linked to AMD. Through gene ontology enrichment analysis with ClueGO in Cytoscape, we determined that several genes in the 1-HLOD support interval of the chromosome 8 locus are involved in fatty acid binding and triglyceride catabolic processes, and the 1-HLOD support interval of the linkage region on chromosome 18 is enriched in genes that participate in serine-type endopeptidase inhibitor activity and the positive regulation of epithelial to mesenchymal transition. These results nominate novel variants and loci for AMD that require further investigation.


Assuntos
Amish/genética , Predisposição Genética para Doença , Variação Genética , Degeneração Macular/genética , Locos de Características Quantitativas , Idoso , Idoso de 80 Anos ou mais , Alelos , Biologia Computacional , Feminino , Frequência do Gene , Ontologia Genética , Estudos de Associação Genética , Ligação Genética , Humanos , Indiana , Masculino , Ohio , Linhagem
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(7): 704-707, 2019 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-31302916

RESUMO

OBJECTIVE: To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy. METHODS: Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed. RESULTS: The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo. CONCLUSION: A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.


Assuntos
Deficiências do Desenvolvimento/genética , Epilepsia/genética , Deficiência Intelectual/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Deleção de Sequência , Criança , Estudos de Associação Genética , Humanos , Cariotipagem
12.
Cytogenet Genome Res ; 158(3): 121-125, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31315107

RESUMO

VACTERL association is defined by the occurrence of congenital malformations: vertebral defects, anal atresia, cardiac defects, tracheoesophageal fistula with esophageal atresia, radial and renal dysplasia, and limb defects. No genetic alterations have been discovered except for some sporadic chromosomal rearrangements and gene mutations. We report a boy with VACTERL association and shawl scrotum with bifid scrotum who presented with a de novo Yq11.223q11.23 microdeletion identified by array CGH. The deletion spans 3.1 Mb and encompasses several genes in the AZFc region, frequently deleted in infertile men with severe oligozoospermia or azoospermia. Herein, we discuss the possible explanation for this unusual genotype-phenotype correlation. We suggest that the deletion of the BPY2 (previously VCY2) gene, located in the AZFc region and involved in spermatogenesis, contributed to the genesis of the phenotype. In fact, BPY2 interacts with a ubiquitin-protein ligase, involved in the SHH pathway which is known to be implicated in the genesis of VACTERL association.


Assuntos
Canal Anal/anormalidades , Deleção Cromossômica , Cromossomos Humanos Y/genética , Esôfago/anormalidades , Cardiopatias Congênitas/genética , Cardiopatias Congênitas/patologia , Rim/anormalidades , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/patologia , Proteínas/genética , Escroto/patologia , Coluna Vertebral/anormalidades , Traqueia/anormalidades , Canal Anal/patologia , Hibridização Genômica Comparativa , Esôfago/patologia , Estudos de Associação Genética , Humanos , Lactente , Rim/patologia , Masculino , Coluna Vertebral/patologia , Traqueia/patologia , Ubiquitina-Proteína Ligases/metabolismo , Incerteza
13.
DNA Cell Biol ; 38(10): 1069-1077, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31361511

RESUMO

Long-noncoding RNA AC092159.2, located ∼247 bp upstream of the TMEM18 gene, may play integral roles in metabolic processes, including adipocyte differentiation and glycometabolism. AC092159.2 may be an important regulator of TMEM18, which is an important susceptibility gene related to obesity and type 2 diabetes. We designed a case-control study (including 964 gestational diabetes mellitus [GDM] cases and 1021 controls) to assess the associations of 14 single-nucleotide polymorphisms (SNPs) in AC092159.2 with the GDM risk. Logistic regression analyses showed that rs11127496 A > G, rs12714417 C > T, and rs1320334 A > G conferred a decreased GDM risk in the recessive and additive model, whereas rs11691220 T > C conferred an increased GDM risk in the dominant and additive model. Also, with increasing number of protective alleles of the four SNPs, the risk of GDM was significantly decreased in a dose-dependent manner (ptrend = 0.007). Further function annotation indicated that these four SNPs may fall on the function elements of human pancreatic islets. The genotype-phenotype associations suggested that these SNPs may contribute to GDM by affecting TMEM18 expression. AC092159.2 SNPs (rs11127496 A > G, rs11691220 T > C, rs12714417 C > T, and rs1320334 A > G) may be susceptibility makers for risk of GDM in Chinese females.


Assuntos
Diabetes Gestacional/genética , Ilhotas Pancreáticas/metabolismo , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Adulto , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/etnologia , Diabetes Gestacional/patologia , Feminino , Regulação da Expressão Gênica , Estudos de Associação Genética , Humanos , Ilhotas Pancreáticas/patologia , Proteínas de Membrana/metabolismo , Modelos Genéticos , Gravidez , RNA Longo não Codificante/metabolismo , Risco
14.
Autoimmun Rev ; 18(9): 102349, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31323359

RESUMO

Myasthenia gravis (MG) is a rare autoimmune disease characterized by muscle weakness and abnormal fatigability. Like many other autoimmune diseases, genetic contribution to MG has been studied where the HLA system appears to play the most vital role. Although many correlations have been revealed in these studies, the underlying mechanism for them is still in the veil. Based on current evidence, we propose two synergetic mechanisms underlying the MG predisposition via HLA. In brief, the first advocates specific MHC II-peptide patterns that influence the efficacy of antigen presentation, and the second emphasizes the role of classical MHC alleles in shaping the TCR repertoire for MG predisposition. Besides, possible explanations for unresolved or controversial MG-related epidemiological phenomenon or clinical problems are addressed as well. Then, we discuss three factors influencing the effect of HLA on MG: gender discrepancy, inflammatory microenvironment, and epigenetic regulation. Lastly, from a provisional angle, we introduce several precautious treatments for people highly predisposed to MG. Although this is a review focusing on MG, the underlying mechanisms might be applicable in other autoimmune diseases as well.


Assuntos
Antígenos HLA/fisiologia , Miastenia Gravis/genética , Alelos , Microambiente Celular/genética , Microambiente Celular/imunologia , Epigênese Genética/fisiologia , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Antígenos HLA/genética , Humanos , Miastenia Gravis/epidemiologia , Miastenia Gravis/imunologia , Miastenia Gravis/terapia , Fatores Sexuais , Transdução de Sinais
15.
Medicine (Baltimore) ; 98(26): e16131, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261535

RESUMO

BACKGROUND: The FOS gene is located on human chromosome 14q21-31 and encodes the nuclear oncoprotein c-Fos. This study analyzed the correlation between the FOS noncoding region rs7101 and rs1063169 polymorphisms and colorectal cancer susceptibility and prognosis. METHODS: We analyzed the FOS genotypes in 432 colorectal cancer patients and 315 healthy subjects by PCR/Sanger sequencing. Survival was analyzed by Kaplan-Meier and Cox regression analysis. Western blot was used to detect the expression of c-Fos protein in cancer tissues and adjacent tissues in colorectal cancer patients with different genotypes. RESULTS: The presence of a T allele at rs7101 and a T allele at rs1063169 in FOS carried a higher risk of colorectal cancer [adjusted odds ratio (OR) = 1.237, 95% confidence interval (95% CI) = 1.131-1.346, P ≤ .001 and adjusted OR = 1.218, 95% CI = 1.111-1.327, P ≤ .001, respectively]. c-Fos protein levels were significantly higher in variant cancer tissues than in normal mucosa tissues (P < .05), and c-Fos proteins levels were also higher in homozygous variant cancer tissues than in heterozygous variant cancer tissues. The 3-year survival rate of patients with wild-type FOS was higher than that of patients with variant FOS (P < .05). CONCLUSION: The rs7101 and rs1063169 polymorphisms in the noncoding region of FOS are associated with the risk of developing colorectal cancer and the progression of colorectal cancer, which may be because the mutation enhances the expression of c-Fos protein to promote the incidence and development of colorectal cancer.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Seguimentos , Expressão Gênica , Interação Gene-Ambiente , Estudos de Associação Genética , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida
16.
Medicine (Baltimore) ; 98(26): e16170, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261547

RESUMO

OBJECTIVE: Non-syndromic cleft of the lip and/or palate (NSCL/P) is one of the most common polygenic diseases. In this study, both case-control and family-based association study were used to confirm whether the Single Nucleotide Polymorphisms (SNPs) were associated with NSCL/P. METHODS: A total of 37 nuclear families and 189 controls were recruited, whose blood DNA was extracted and subjected to genotyping of SNPs of 27 candidate genes by polymerase chain reaction-improved multiple ligase detection reaction technology (PCR-iMLDR). Case-control statistical analysis was performed using the SPSS 19.0. Haplotype Relative Risk (HRR), transmission disequilibrium test (TDT), and Family-Based Association Test (FBAT) were used to test for over-transmission of the target alleles in case-parent trios. The gene-gene interactions on NSCL/P were analyzed by Unphased-3.1.4. RESULTS: In case-control statistical analysis, only C14orf49 chr14_95932477 had statistically significant on genotype model (P = .03) and allele model (P = .03). Seven SNPs had statistically significant on TDT. None of 26 alleles has association with NSCL/P on FBAT. Some SNPs had haplotype-haplotype interactions and genotype-genotype interactions. CONCLUSION: C14orf49 chr14_95932477 was significantly different between cases and controls on genotype model and allele model by case-control design. Seven SNPs were significantly different on HRR. Four SNPs were significantly different on TDT.


Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Fenda Labial/complicações , Fissura Palatina/complicações , Família , Feminino , Estudos de Associação Genética , Humanos , Masculino , Modelos Genéticos , Fosfatases de Fosfoinositídeos/genética , Proteínas de Transporte Vesicular/genética
17.
Psychiatr Danub ; 31(2): 269-275, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31291236

RESUMO

BACKGROUND: Posttraumatic stress disorder (PTSD) is a highly frequent and disabling psychiatric condition among war-affected populations. The FK506-binding protein 5 (FKBP5) gene and the corticotropin-releasing hormone receptor 1 (CRHR1) gene have previously been implicated in an elevated risk of peritraumatic dissociation and PTSD development. Our aim was to investigate the association between FKBP5 and CRHR1 genotypes and PTSD diagnosis and severity among individuals who were affected by the Balkan wars during the 1990s. SUBJECTS AND METHODS: This study included participants with current PTSD, remitted PTSD and healthy volunteers (N=719, 487 males), who were recruited between 2013 and 2015 within the framework of the South Eastern Europe (SEE) - PTSD Study. Psychometric methods comprised the Mini International Neuropsychiatric Interview (M.I.N.I.), the Clinician Administrated PTSD Scale (CAPS), and the Brief Symptom Inventory (BSI). FKBP5 rs1360780 and CRHR1 rs17689918 genotypes were determined using a KASP genotyping assay. RESULTS: Tests for deviation from Hardy Weinberg equilibrium showed no significant results. Logistic and linear regression was used to examine the associations between the FKBP5 SNP rs1360780 and the CRHR1 SNP rs17689918 with PTSD diagnosis and severity, as well as general psychiatric symptom severity, separately for current and remitted PTSD patients. There were nominally significant associations under a dominant model between the rs1360780 C allele and PTSD diagnosis as well as symptom severity, which however, were not significant anymore after Bonferroni adjustment (α=0.002). For CRHR1 rs17689918 no significant associations were detected. CONCLUSION: We found nominally, but not Bonferroni corrected significant associations between the FKBP5 polymorphism rs1360780 and PTSD susceptibility among individuals affected by the Balkan wars. For elucidating this gene's real resilience/vulnerability potential, environmental influences should be taken into account.


Assuntos
Conflitos Armados/psicologia , Estudos de Associação Genética , Polimorfismo de Nucleotídeo Único , Receptores de Hormônio Liberador da Corticotropina/genética , Transtornos de Estresse Pós-Traumáticos/genética , Proteínas de Ligação a Tacrolimo/genética , Europa Oriental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Am J Orthod Dentofacial Orthop ; 156(1): 104-112.e3, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256822

RESUMO

INTRODUCTION: Mandibular prognathism (MP) is subject to major polygenic influence and segregates within families in autosomal dominance with variable expressivity and incomplete penetrance. We aimed to identify the inheritance pattern and genes and loci involved in the development of MP in Mediterranean families and to evaluate the dentoskeletal characteristics of affected individuals. METHODS: Fifty-one eastern Mediterranean families with individuals affected by MP were identified. Data and biospecimens were collected from 14 of the families, including clinical examination, lateral cephalography (on subjects with Class III malocclusion), and 5 mL blood drawn from consenting affected and nonaffected relatives. Next-generation sequencing (NGS) was performed on 8 families (7 Lebanese, 1 Lebanese/Syrian), including large numbers of affected individuals over many generations and severe conditions, with the use of whole-exome sequencing. RESULTS: Most pedigrees suggested autosomal-dominant inheritance with an equal number of affected male and female individuals. Affected individuals had macrognathic and prognathic mandibles with dentoalveolar compensation. Genetic screening did not correspond with previously reported MP-linked genes, but yielded 3 novel genes (C1orf167, NBPF8, NBPF9) on chromosome 1 potentially responsible for mandibular development and macrognathism. CONCLUSIONS: In this first genetic study with the use of NGS on the largest reported number of families with MP, novel genes (C1orf167, NBPF8, NBPF9) were associated with familial MP in the eastern Mediterranean population.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença/genética , Má Oclusão de Angle Classe III/genética , Prognatismo/genética , Adulto , Grupo com Ancestrais do Continente Asiático , Cefalometria , Cromossomos Humanos Par 1/genética , Feminino , Genoma Humano , Humanos , Líbano , Masculino , Má Oclusão de Angle Classe III/sangue , Má Oclusão de Angle Classe III/diagnóstico por imagem , Má Oclusão de Angle Classe III/patologia , Pessoa de Meia-Idade , Linhagem , Prognatismo/sangue , Prognatismo/diagnóstico por imagem , Prognatismo/patologia , Análise de Sequência de DNA , Síria , Adulto Jovem
19.
BMC Plant Biol ; 19(1): 332, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31357930

RESUMO

BACKGROUND: Good establishment is important for rapid leaf area development in wheat crops. Poor establishment results in fewer, later-emerging plants, reduced leaf area and tiller number. In addition, poorly established crops suffer from increased soil moisture loss through evaporation and greater competition from weeds while fewer spikes are produced which can reduce grain yield. By protecting the emerging first leaf, the coleoptile is critical for achieving good establishment, and its length and interaction with soil physical properties determine the ability of a cultivar to emerge from depth. RESULTS: Here we characterise a locus on chromosome 1AS, that increases coleoptile length in wheat, which we designate as Lcol-A1. We identified Lcol-A1 by bulked-segregant analysis and used a Halberd-derived population to fine map the gene to a 2 cM region, equivalent to 7 Mb on the IWGSC genome reference sequence of Chinese Spring (RefSeqv1.0). By sowing recently released cultivars and near-isogenic lines in the field at both conventional and deep sowing depths, we confirmed that Locl-A1 was associated with increased emergence from depth in the presence and absence of conventional dwarfing genes. Flanking markers IWB58229 and IWA710 were developed to assist breeders to select for long coleoptile wheats. CONCLUSIONS: Increased coleoptile length is sought in many global wheat production areas to improve crop emergence. The identification of the gene Lcol-A1, together with tools to allow wheat breeders to track the gene, will enable improvements to be made for this important trait.


Assuntos
Cotilédone/crescimento & desenvolvimento , Genes de Plantas/fisiologia , Triticum/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Genes de Plantas/genética , Estudos de Associação Genética , Loci Gênicos , Folhas de Planta/crescimento & desenvolvimento , Polimorfismo de Nucleotídeo Único/genética , Característica Quantitativa Herdável , Triticum/crescimento & desenvolvimento
20.
BMC Bioinformatics ; 20(1): 404, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31345171

RESUMO

BACKGROUND: It has been shown that the deregulation of miRNAs is associated with the development and progression of many human diseases. To reduce time and cost of biological experiments, a number of algorithms have been proposed for predicting miRNA-disease associations. However, the existing methods rarely investigated the cause-and-effect mechanism behind these associations, which hindered further biomedical follow-ups. RESULTS: In this study, we presented a CCA-based model in which the possible molecular causes of miRNA-disease associations were comprehensively revealed by extracting correlated sets of genes and diseases based on the co-occurrence of miRNAs in target gene profiles and disease profiles. Our method directly suggested the underlying genes involved, which could be used for experimental tests and confirmation. The inference of associated diseases of a new miRNA was made by taking into account the weight vectors of the extracted sets. We extracted 60 pairs of correlated sets from 404 miRNAs with two profiles for 2796 target genes and 362 diseases. The extracted diseases could be considered as possible outcomes of miRNAs regulating the target genes which appeared in the same set, some of which were supported by independent source of information. Furthermore, we tested our method on the 404 miRNAs under the condition of 5-fold cross validations and received an AUC value of 0.84606. Finally, we extensively inferred miRNA-disease associations for 100 new miRNAs and some interesting prediction results were validated by established databases. CONCLUSIONS: The encouraging results demonstrated that our method could provide a biologically relevant prediction and interpretation of associations between miRNAs and diseases, which were of great usefulness when guiding biological experiments for scientific research.


Assuntos
Algoritmos , Biologia Computacional/métodos , Doença/genética , Estudos de Associação Genética , MicroRNAs/genética , Bases de Dados Genéticas , Humanos , MicroRNAs/metabolismo , Modelos Genéticos
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