RESUMO
This study aimed to determine the role of mitofusin 2 (MFN2) gene polymorphisms in the risk and prognosis of acute liver failure (ALF). A total of 298 blood samples were collected from 138 ALF patients (case group) and 160 healthy participants (control group). Coagulation function, glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), total bilirubin (TB), blood ammonia and lactic acid (LA) were measured. The predictive evaluation of MFN2 gene polymorphisms in the risk and prognosis of ALF patients was estimated using Kaplan-Meier survival analysis, haplotype analysis, binary logistic regression analysis and Cox regression analysis. Higher levels of GPT, GOT, TB, blood ammonia and LA were observed in ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 than in those with the CC genotype of these two SNPs. The GTACAGC and GTGTGGC haplotypes were a protective factor and a risk factor for ALF, respectively. Blood ammonia and LA levels were independent risk factors and the CC genotype of rs873457 and the CC genotype of rs4846085 were protective factors for ALF. ALF patients with the GG genotype of rs873457 or the TT genotype of rs4846085 had a lower survival rate than those with other genotypes of these two SNPs. The rs4846085 and rs873457 polymorphisms were both independent factors affecting the prognosis of ALF patients. MFN2 gene polymorphisms (rs873457, rs2336384, rs1474868, rs4846085 and rs2236055) may be associated with ALF and the rs873457 and rs4846085 polymorphisms are correlated with the risk and prognosis of ALF.
Assuntos
GTP Fosfo-Hidrolases/genética , Falência Hepática Aguda/genética , Proteínas Mitocondriais/genética , Polimorfismo de Nucleotídeo Único , Adulto , Amônia/sangue , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Hepatite A/genética , Humanos , Estimativa de Kaplan-Meier , Ácido Láctico/sangue , Falência Hepática Aguda/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Adulto JovemRESUMO
Birth defects are structural and/or functional malformations present at birth that cause physical or mental disability and are important public health problems. Our study was aimed at genetic analysis and prenatal diagnosis of congenital anomalies to understand the cause of certain birth defects. Karyotypes and array-comparative genomic hybridization (aCGH) were performed on a pregnant woman, surrounding amniotic fluid, and her husband. A short-stature panel genetic test was conducted in accordance with the phenotype of the fetus. Following examination, it was determined that the karyotype and aCGH results were normal. The RECQL4 gene in the fetus showed compound heterozygous mutations, and each parent was found to be a carrier of one of the mutations. The two heterozygous mutations (c.2059-1G>C and c.2141_2142delAG) were detected in the RECQL4 (NM_004260) gene in the fetus; therefore, the fetus was predicted to have Baller-Gerold syndrome. These two mutations have not previously been reported. In addition, these results identified a 25% risk of the parents having a sec-ond conceptus with this congenital disease. Therefore, prenatal genetic diagnosis was highly recommended for future pregnancies.
Assuntos
Craniossinostoses/diagnóstico , Heterozigoto , Mutação , Rádio (Anatomia)/anormalidades , RecQ Helicases/genética , Adulto , Hibridização Genômica Comparativa , Craniossinostoses/genética , Feminino , Humanos , Cariotipagem , Masculino , Gravidez , Diagnóstico Pré-NatalRESUMO
Infection is the leading risk factor of liver transplantation-related death. Aspergillosis is a life-threatening complication in immune-compromised patients, and is the cause of approximately 2/3 of deaths in liver transplant recipients. In our previous studies, we found a regulatory T cell (Treg) population that showed significantly increased immune tolerance in Aspergillus-infected liver transplant recipients. Furthermore, interleukin (IL)-17 production was also increased, and an IL-17-producing Treg cell subset was identified in these patients. Functional studies of the role of these IL-17-producing Treg cells in the induction of immune tolerance are needed to help reduce the death rate of liver transplantation recipients. This study included 75 liver transplant recipients with and without histologically confirmed aspergillosis after liver transplantation. The percentage of T cell population subsets producing cytokines was detected by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay in peripheral blood. Complements in blood serum were also examined. The risk of acute rejection was lower in Aspergillus-infected liver transplant recipients compared to the non-Aspergillus-infected group; the CD4(+)CD25(hi) T cell population in peripheral blood was higher and the CD4(+)CD45RA-CD45RO(+) T cell population was lower. There was no significant difference between the CD4(+)CD25(lo)CD45RA(+) and CD4(+)CD25(lo)CD45RA- T cell populations. Moreover, IL-6 decreased and IL-4 increased in the blood serum of Aspergillus-infected liver transplant recipients. Together, these results indicate that the incidence of graft rejection in liver transplantation recipients with Aspergillus infections was lower than that of the non-infected group, and suggests a mechanism for this effect.
Assuntos
Aspergilose/imunologia , Aspergillus/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Fígado , Subpopulações de Linfócitos T/imunologia , Adulto , Aspergilose/microbiologia , Antígenos CD4/genética , Antígenos CD4/imunologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Subunidade alfa de Receptor de Interleucina-2/genética , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-4/agonistas , Interleucina-4/biossíntese , Interleucina-4/sangue , Interleucina-6/antagonistas & inibidores , Interleucina-6/biossíntese , Interleucina-6/sangue , Antígenos Comuns de Leucócito/genética , Antígenos Comuns de Leucócito/imunologia , Fígado/imunologia , Fígado/microbiologia , Fígado/patologia , Fígado/cirurgia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/microbiologiaRESUMO
Retinoid X receptors (RXR) are members of the nuclear receptor family that are conserved from invertebrates to vertebrates, and they play an essential role in regulating reproductive maturation, molting, and embryo development. In this study, five RXR isoforms, named RXRL2 (L, long form), RXRL3, RXRS1 (S, short form), RXRS2, and RXRS3, containing six domains from A to F, were cloned from the prawn Macrobrachium nipponense using 5'- and 3'- rapid amplification of cDNA ends. Differences among their structures were observed not only in the D and E domains but also in the A/B domain, which were previously found in insects but not in crustaceans. This is the first report to show that differences occur in the A/B domain of RXR in crustaceans. RXR expressions were also examined in various tissues including the ovary, testis, muscle, hepatopancreas, heart, gill, stomach, intestine, and cuticle. Expression pattern investigations indicated that the five isoforms were differentially expressed. RXRS3 was only detected in the ovary, and the other RXRs were abundant in the ovary and testis. These data suggested that RXR mediates a series of processes related to reproduction.