RESUMO
The incidence of papillary thyroid carcinoma (PTC) is increasing rapidly throughout the world. Hence, there is an urgent need for identifying more specific and sensitive biomarkers to explorate the pathogenesis of PTC. In this study, three pairs of stage I PTC tissues and matched normal adjacent tissues were sequenced by RNA-Seq, and 719 differentially expressed genes (DEGs) were screened. KEGG pathway enrichment analyses indicated that the DEGs were significantly enriched in 28 pathways. A total of 18 nodes consisting of 20 DEGs were identified in the top 10% of KEGG integrated networks. The functions of DEGs were further analysed by GO. The 13 selected genes were confirmed by qRT-PCR in 16 stage I PTC patients and by The Cancer Genome Atlas (TCGA) database. The relationship interactions between DEGs were analysed by protein-protein interaction networks and chromosome localizations. Finally, four newly discovered genes, COMP, COL3A1, ZAP70, and CD247, were found to be related with PTC clinical phenotypes, and were confirmed by Spearman's correlation analyses in TCGA database. These four DEGs might be promising biomarkers for early-stage PTC, and provide an experimental foundation for further exploration of the pathogenesis of early-stage PTC.
Assuntos
Biomarcadores Tumorais/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Proteína de Matriz Oligomérica de Cartilagem/genética , Mapeamento Cromossômico , Colágeno Tipo III/genética , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Humanos , Mapas de Interação de Proteínas , Reprodutibilidade dos Testes , Transdução de Sinais/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Proteína-Tirosina Quinase ZAP-70/genéticaRESUMO
BACKGROUND: A study has identified several novel susceptibility variants of the mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) gene for type 2 diabetes mellitus (T2DM) within the German population. Among the variants, five single nucleotide polymorphisms (SNPs) of MAP4K4 (rs1003376, rs11674694, rs2236935, rs2236936, and rs6543087) showed significant association with T2DM or diabetes-related quantitative traits. We aimed to evaluate whether common SNPs in the MAP4K4 gene were associated with T2DM in the Chinese population. METHODS: Five candidate SNPs were genotyped in 996 patients newly diagnosed with T2DM and in 976 control subjects, using the SNPscan™ method. All subjects were recruited from the Second Affiliated Hospital, Harbin Medical University from October 2010 to September 2013. We evaluated the T2DM risk conferred by individual SNPs and haplotypes using logistic analysis, and the association between the five SNPs and metabolic traits in the subgroups. RESULTS: Of the five variants, SNP rs2236935T/C was significantly associated with T2DM in this study population (odds ratio = 1.293; 95% confidence interval: 1.034-1.619, P= 0.025). In addition, among the controls, rs1003376 was significantly associated with an increased body mass index (P = 0.045) and homeostatic model assessment-insulin resistance (P = 0.037). CONCLUSIONS: MAP4K4 gene is associated with T2DM in a Chinese Han population, and MAP4K4 gene variants may contribute to the risk toward the development of T2DM.
Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Povo Asiático , Feminino , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
UBE2E2 encodes ubiquitin-conjugating enzyme E2E2, which plays an important role in the synthesis and secretion of insulin. Two previous studies indicated that SNPs in UBE2E2 were associated with risk for type 2 diabetes mellitus (T2DM) in the Japanese and Korean populations, respectively. We examined the association of one SNP in this gene, rs7612463, with the risk of T2DM in 1957 Han participants in northeastern China, using an SNPscan(TM) Kit. rs7612463 genotype was significantly associated with risk for T2DM under various genetic models, including an additive model (P = 0.004), a dominant model (P = 0.024), and a recessive model (P = 0.008). The AA genotype was associated with a significantly decreased risk for T2DM (P = 0.004, OR = 0.513, 95% CI = 0.325-0.810) after adjustment for age, gender, and BMI. The heterozygous genotype, AC, was associated with increased risk for total cholesterol (mmol l-1; P = 0.031) and triglycerides (mmol l-1; P = 0.039) in control individuals. Our results show that rs7612463 is associated with T2DM, with homozygotes of the AA genotype at decreased risk for T2DM in the Chinese population. Additionally, heterozygotes may have decreased risk of T2DM due to insulin resistance.
