RESUMEN
BACKGROUND: The single nucleotide polymorphism (SNP) rs2476601 of the protein tyrosine phosphatase, nonreceptor type 22 (PTPN22) gene has been presented to implicate in the pathogenesis of alopecia areata (AA) in a few association investigations with limited sample size and inconsistent conclusions. METHODS: The aim of the current meta-analysis was to assess and synthesize the presently available data on the connection between rs2476601 and AA vulnerability. Six electronic databases, including EMBASE, PubMed, Web of Science, the Cochrane Library, Wanfang data, and the China National Knowledge Infrastructure database (CNKI), were systematically retrieved for relevant observational studies published previous to November 2018. Total odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were analyzed to evaluate the correlation between PTPN22 polymorphism and AA. Risk of bias was estimated according to the Newcastle-Ottawa Scale (NOS). Sensitivity analyses were carried out using the RevMan 5.3 software. RESULTS: In general, 5 case-control studies including 1129 AA patients and 1702 healthy control individuals were obtained for this meta-analysis. The pooled results suggested that rs2476601 SNP was significantly associated with AA susceptibility under allelic model (C vs T, ORâ=â0.77, 95% CI, 0.64-0.92, Pâ=â.003) and recessive model (CC vs CT + TT, ORâ=â0.73, 95% CI, 0.60-0.88, Pâ=â.001). CONCLUSION: On the basis of the results of the current research, the rs2476601 polymorphism of PTPN22 gene is significantly correlated with AA susceptibility. The C-allele and CC-genotype carriers at this locus have a lower risk of AA.
Asunto(s)
Alopecia Areata/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 22/genética , Alelos , Alopecia Areata/etnología , Alopecia Areata/fisiopatología , Estudios de Casos y Controles , Femenino , Genotipo , Heterocigoto , Humanos , Masculino , Estudios Observacionales como Asunto , Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: To explore the changes in gene expression of bone in endotoxemia in mice. METHODS: Lipopolysaccharide (LPS) was injected intraperitoneally to reproduce an endotoxemia model in mice. Forty-eight mice were randomly divided into eight groups: normal group, 4, 6, 8, 12, 24, 48 and 72 hours after LPS injection groups, with 6 mice in each group. To evaluate endotoxemia whole blood was collected for leukocytic count, eye sockets blood was obtained for liver and renal functions tests. mRNA expression level of Toll-like receptor 4 (TLR4) in bone was determined by reverse transcription-polymerase chain reaction (RT-PCR) assay. The pathological changes of bone and tissue slides were prepared with hematoxylin and eosin (HE) staining for observing under microscope. RESULTS: Compared with normal group, leukocyte count of 4-hour LPS-treated group was significantly decreased (P<0.01). However, after 4 hours, leukocyte count became higher gradually and remained at high level at 72 hours compared with that of normal group (P<0.05). Compared with normal group, alanine aminotransferase (ALT) level reached to a high level in LPS-treated groups at 4 hours and 6 hours (both P<0.05), and then decreased gradually showing a tendency to return to normal level after 8 hours (P>0.05). Blood urea nitrogen (BUN) was increased at 6 hours (P<0.05), reaching to the highest level at 8 hours (P<0.05) and tended to become normal level after 12 hours (P>0.05). Six hours after LPS treatment, the expression of TLR4 mRNA was enhanced (P<0.01) and reached the peak at 24 hours (P<0.01), and it remained at a high level at 72 hours (P<0.05). However, there were no significant pathological changes in bone structure after LPS treatment. CONCLUSION: Expression level of TLR4 mRNA in bone is significantly increased in endotoxemia mice.