RESUMO
Long QT syndrome (LQTS) is known to be involved in some sudden unexplained death (SUD) cases. To make clear whether the pathogenic genes of LQTS are involved in SUD in Yunnan province, southwest of China, we examined 4 mutation hotspot segments of KCNQ1, KCNH2, and SCN5A genes in 83 SUD cases using polymerase chain reaction and direct DNA sequencing. Genomic DNA was extracted from paraffin-embedded tissues in 83 cases of sudden cardiac death. One novel homozygous missense variant was identified in exon 3 of KCNQ1, c. 575G>T (p.R192L) in one case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1789T>A (p.Y597N) in 1 case. One novel heterozygous missense variant was identified in exon 7 of KCNH2, c.1800C>A (p.S600R) in 9 cases. In addition, 18 individuals were found to have heterozygous missense variant in exon 7 of KCNH2, c.1801G>A (p.G601S). Our study suggests that some SUDs in Yunnan province may be related with the pathogenic genes of LQTS.
Assuntos
Morte Súbita Cardíaca/etiologia , Canal de Potássio ERG1/genética , Canal de Potássio KCNQ1/genética , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Adulto , Povo Asiático/genética , China , Éxons , Feminino , Genética Forense , Heterozigoto , Humanos , Síndrome do QT Longo/genética , Masculino , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
To explore the association of polymorphism in the serotonin transporter gene and the susceptibility to alcohol dependence in Yunnan Han population, PCR and DNA sequencing techniques were used to detect 5-HTT-linked promoter region (5-HTTLPR). One hundred and eighteen alcohol dependent patients as case group and 214 normal people as control group were employed in this study. Significant differences in genotype frequencies were present between case group and control group of 5-HTTLPR (P<0.05). The proportion of L/L and L/S genotype was significantly smaller in case group than that was in control group (OR=0.581, P=0.026). No significant association was observed in allelic frequencies, which differed in different ethnic groups. In conclusion, 5-HTTLPR polymorphism may be associated with alcohol dependent patients, and the genotype L/L or L/S may be a genetic factor that is responsible for decreasing susceptibility of alcohol dependence in Yunnan Han population.
Assuntos
Alcoolismo/genética , Predisposição Genética para Doença , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Adulto , Idoso , China/etnologia , Humanos , Pessoa de Meia-Idade , Regiões Promotoras GenéticasRESUMO
The enzyme catechol-O-methyltransferase (COMT) transfers a methyl group from S-adenosylmethionine to the benzene ring of catecholamines including the neurotransmitters dopamine, epinephrine and norepinephrine. This methylation results in the degradation of catecholamines. The involvement of the COMT gene in the metabolic pathway of these neurotransmitters has made it an attractive candidate gene for many psychiatric disorders. This review focuses on the association between the genetic polymorphisms of COMT gene and psychiatric disorders.
Assuntos
Catecol O-Metiltransferase/genética , Transtornos Mentais/genética , Polimorfismo Genético , HumanosRESUMO
A new L-amino acid oxidase (designated as DRS-LAAO) was purified from Daboia russellii siamensis venom by ion-exchange, gel filtration and affinity chromatographies. DRS-LAAO is a homodimeric enzyme with a molecular weight of 120.0 kDa as measured by size exclusion chromatography and the monomeric molecular weight of 58.0 kDa as measured by SDS-PAGE under both non-reducing and reducing conditions. The N-terminal amino acid sequence (ADDKNPLEECFREDD) of DRS-LAAO shares high identity with other snake venom L-amino acid oxidases, especially with those isolated from viperid venoms. The enzyme displayed high specificity towards hydrophobic L-amino acids. The best substrate of DRS-LAAO was L-Leu followed by L-Phe and L-Ile, while five substrates--L-Pro, L-Asn, L-Gly, L-Ser and L-Cys were not oxidized. Optimal pH of DRS-LAAO was 8.8. The enzyme showed no hemorrhagic activity even at a dosage of 55.0 microg. DRS-LAAO dose-dependently inhibited platelet aggregation induced by ADP (83.33 microM) and TMVA (55.0 nM) with an IC(50) value of 32.8 microg/ml and 32.3 microg/ml, respectively. The minimum inhibitory concentrations (MICs) of DRS-LAAO against Staphylococci aureus (ATCC 25923), Pseudomonas aeruginosa (ATCC 27853) and Escherichia coli (ATCC 25922) were 9.0, 144.0 and 288.0 microg/ml, respectively. The minimum bactericidal concentrations (MBCs) of the enzyme for these strains were twice of the MIC values. These results showed that DRS-LAAO had the strongest antimicrobial activity against S. aureus among these three international standard stains. Antibacterial-activities of DRS-LAAO against eight clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates were also tested. The MICs of DRS-LAAO against these isolates ranged from 4.5 to 36.0 microg/ml. And the MBCs of the enzyme against these isolates ranged from 9.0 to 72.0 microg/ml.
Assuntos
L-Aminoácido Oxidase/isolamento & purificação , Venenos de Víboras/enzimologia , Sequência de Aminoácidos , Cromatografia em Gel , Eletroforese em Gel de Poliacrilamida , Escherichia coli/efeitos dos fármacos , Humanos , L-Aminoácido Oxidase/química , L-Aminoácido Oxidase/farmacologia , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Agregação Plaquetária/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Especificidade por SubstratoRESUMO
Alcohol dependence is a complex disorder which is influenced by physiological, psychological, environmental factors, individual inheritance and so on. Several candidate genes associated with alcohol dependence risk have been identified. The review focuses on several related genes that control alcohol metabolism such as alcohol dehydrogenase, aldehyde dehydrogenase, cytochrome P450 2E1 and regulate neurotransmission such as catechol-O-methyltransferase, dopamine receptors D2 and D4, and mu opioid receptor.
Assuntos
Alcoolismo/genética , Polimorfismo Genético/genética , Álcool Desidrogenase/genética , Aldeído Desidrogenase/genética , Catecol O-Metiltransferase/genética , Citocromo P-450 CYP2E1/genética , Humanos , Receptores de Dopamina D2/genéticaRESUMO
A novel C-type lectin-like protein, dabocetin, was purified from Daboia russellii siamensis venom. On SDS-polyacrylamide gel electrophoresis, it showed a single band with an apparent molecular weight of 28 kDa and two distinct bands with the apparent molecular weights of 15.0 kDa and 14.5 kDa under non-reducing and reducing conditions, respectively. cDNA clones containing the coding sequences for dabocetin alpha and beta subunits were isolated and sequenced. The deduced protein sequences of both subunits were confirmed by N-terminal amino acid sequencing and trypsin-digested peptide mass fingerprinting. Dabocetin did not induce platelet aggregation in platelet-rich plasma. It also had little effect on the platelet aggregation induced by ADP, TMVA or stejnulxin. Whereas, dabocetin inhibited ristocetin-induced platelet agglutination in platelet-rich plasma in a dose-dependent manner with an IC50 value of 0.35 microM. Flow cytometry analysis showed that dabocetin significantly inhibited mAb SZ2 binding to platelet membrane glycoprotein Ib alpha, indicating that platelet membrane glycoprotein Ib is involved in the inhibitory effect of dabocetin on ristocetin-induced platelet agglutination.
