RESUMO
BACKGROUND: The human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population. METHODS: Conditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues. RESULTS: Of the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (Pâ=â6.07E-06, ORâ=â1.71, 95%CIâ=â1.36-2.17), rs3763338 (Pâ=â1.62E-05, ORâ=â0.63, 95%CIâ=â0.50-0.78) and rs2844695 (Pâ=â7.60E-05, ORâ=â0.74, 95%CIâ=â0.64-0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (Pâ=â0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (Pâ=â0.001) and family history (P<0.001). CONCLUSION: This study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.
Assuntos
Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Complexo Principal de Histocompatibilidade/genética , Polimorfismo de Nucleotídeo Único/genética , Carcinoma de Células Escamosas/patologia , China/epidemiologia , Proteínas de Ligação a DNA/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Técnicas de Genotipagem , Cadeias alfa de HLA-DQ/genética , Humanos , Imuno-Histoquímica , Incidência , Desequilíbrio de Ligação/genética , Modelos Logísticos , Proteínas Nucleares/genética , Controle de Qualidade , Fatores de RiscoRESUMO
We performed a genome-wide association study of esophageal squamous cell carcinoma (ESCC) by genotyping 1,077 individuals with ESCC and 1,733 control subjects of Chinese Han descent. We selected 18 promising SNPs for replication in an additional 7,673 cases of ESCC and 11,013 control subjects of Chinese Han descent and 303 cases of ESCC and 537 control subjects of Chinese Uygur-Kazakh descent. We identified two previously unknown susceptibility loci for ESCC: PLCE1 at 10q23 (P(Han combined for ESCC) = 7.46 x 10(-56), odds ratio (OR) = 1.43; P(Uygur-Kazakh for ESCC) = 5.70 x 10(-4), OR = 1.53) and C20orf54 at 20p13 (P(Han combined for ESCC) = 1.21 x 10(-11), OR = 0.86; P(Uygur-Kazakh for ESCC) = 7.88 x 10(-3), OR = 0.66). We also confirmed association in 2,766 cases of gastric cardia adenocarcinoma cases and the same 11,013 control subjects (PLCE1, P(Han for GCA) = 1.74 x 10(-39), OR = 1.55 and C20orf54, P(Han for GCA) = 3.02 x 10(-3), OR = 0.91). PLCE1 and C20orf54 have important biological implications for both ESCC and GCA. PLCE1 might regulate cell growth, differentiation, apoptosis and angiogenesis. C20orf54 is responsible for transporting riboflavin, and deficiency of riboflavin has been documented as a risk factor for ESCC and GCA.
Assuntos
Povo Asiático/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Loci Gênicos , Proteínas de Membrana/genética , Fosfoinositídeo Fosfolipase C/genética , Idoso , Carcinoma de Células Escamosas/etnologia , Estudos de Casos e Controles , Cromossomos Humanos Par 10 , Cromossomos Humanos Par 20 , Neoplasias Esofágicas/etnologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Proteínas de Membrana Transportadoras , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/fisiologiaRESUMO
The near infrared reflectance spectroscopy technique (NIRS) has been explored at many fields such as agriculture, food, chemical, medicine, and so on, due to its rapid, effective, non-destructive, and on-line characteristics. Fungi invasion in forage materials during processing and storage would generate mycotoxins, which were harmful for people and animal through food chains. The determination of mycotoxins included the overelaborated pretreatments such as milling, extracting, chromatography and subsequent process such as enzyme linked immunosorbent assay, high performance liquid chromatography, and thin layer chromatography. The authors hope that high precision and low detection limit spectrum instrument, and software technology and calibration model of mycotoxins determination, will fast measure accurately the quality and quantity of mycotoxins, which will provide basis for reasonable process and utilization of forage and promote the application of NIRS in the safety livestock product.
Assuntos
Ração Animal/análise , Micotoxinas/análise , Espectroscopia de Luz Próxima ao Infravermelho , Agricultura , Ração Animal/microbiologia , Animais , Calibragem , Cromatografia Líquida de Alta Pressão , SoftwareRESUMO
Phospholipid hydroperoxide glutathione peroxidase (PHGPx), as a ubiquitous antioxidant enzyme in the glutathione peroxidases (GPx) family, plays multiple roles in organisms. However, there is very little information on PHGPx in goats (Capra hircus). In this study, a full-length cDNA was cloned and characterized from Taihang black goat testes. The 844 bp cDNA contains an open reading frame (ORF) of 597 bp. The goat PHGPx nucleotide sequence contains a selenocysteine (sec) codon TGA(244-246), two potential start codons ATG(20-22) and ATG(108-110), a polyadenylation signal AATAAA(813-818) and selenocysteine insertion sequence (SECIS) motif AUGA(688-691), UGA(729-731) and AAA(703-705). As a selenoprotein, the active-site motifs and GPx family signature motifs LAFPCNQF(101-108) and WNFEK(165-170) were also found. The order of PHGPx mRNA expression levels was: testes >> heart > brain > epididymis > kidney > liver > lung > spleen > muscle. Real-time PCR and immunohistochemistry results revealed similar expression differences in different age testes, with high expression levels during adolescence. Immunofluorescence results suggested that PHGPx mainly expressed in Leydig cells and spermatids in mature goat testes.
Assuntos
Regulação Enzimológica da Expressão Gênica , Glutationa Peroxidase/metabolismo , Cabras/fisiologia , Testículo/enzimologia , Animais , Clonagem Molecular , Perfilação da Expressão Gênica , Glutationa Peroxidase/genética , Imuno-Histoquímica , Masculino , Fases de Leitura Aberta/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Reação em Cadeia da PolimeraseRESUMO
The objective of this experiment is to study the effects of novel elemental nano-selenium in the diet on testicular ultrastructure, semen quality and GSH-Px activity in male goats. Forty-two 2-month-old bucks were offered a total mixed ration which had been supplemented with nano-Se (0.3mg/kg Se) or unsupplemented (the control group only received 0.06mg/kg Se-background), for a period of 12 weeks (from weaning to sexual maturity). Results showed that the testicular Se level, semen glutathione peroxidase and ATPase activity increased significantly in the nano-Se supplementation group compared with control (P<0.05). The semen quality (volume, density, motility and pH) was not affected by added Se in diets, however, the sperm abnormality rate of control bucks was significantly higher than Se supplemented bucks (P<0.05). The testes of 5 goats in each group were examined by transmission electron microscopy (TEM), and showed that in Se-deficient bucks the membrane was damaged, and showed the occurrence of abnormalities in the mitochondria of the midpiece of spermatozoa. In conclusion, selenium deficiency resulted in abnormal spermatozoal mitochondria, and supplementation with nano-Se enhanced the testis Se content, testicular and semen GSH-Px activity, protected the membrane system integrity and the tight arrayment of the midpiece of the mitochondria. Further studies are required to research the novel elemental nano-Se with characterization of bioavailability and toxicity in small ruminants.
Assuntos
Dieta , Glutationa Peroxidase/metabolismo , Cabras , Selênio/administração & dosagem , Sêmen/fisiologia , Testículo/ultraestrutura , Adenosina Trifosfatases/análise , Animais , Doenças das Cabras/etiologia , Masculino , Microscopia Eletrônica de Transmissão , Necessidades Nutricionais , Selênio/deficiência , Sêmen/enzimologia , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides/anormalidades , Espermatozoides/fisiologia , Espermatozoides/ultraestrutura , Testículo/química , Testículo/enzimologiaRESUMO
A 261 bp sequence of the bovine MyoD gene intron 2 was cloned and was found to bear no similarities to the human MyoD gene sequence. Polymorphisms of the Myod gene in cattle including three Chinese breeds (Luxi cattle, Jinnan cattle and Qinchuan cattle) and four cross-breeding populations (Limousin x Luxi cattle, Simmental x Luxi cattle, Charolais x Luxi cattle and Angus x Luxi cattle) were detected by PCR-SSCP. Two SSCP alleles (A and B) were detected, which caused by a C-->T at 39 bp and a C-->G transition at 112 bp. Only two genotypes AA and AB occurred in the population. In Chinese local cattle, B allele was dominant, and this locus was at Hardy-Weinberg equilibrium except for the Charolais x Luxi cattle and Angus x Luxi cattle. The association of these polymorphisms with cattle carcass traits was analyzed using the general linear model (GLM). Statistical analysis revealed a higher value of living weight, carcass weight and loin eye area for individuals with genotype AA than AB (P < 0.05). Further studies on a bigger population size are needed to confirm the observed effect of MyoD genotypes on carcass quality traits.