RESUMEN
Excessive immune response is believed to play a role in the development of severe acute respiratory syndrome (SARS). Inhomogeneous spread of SARS led one to think of an Asian genetic predisposition and contribution of human leukocyte antigen (HLA) to the disease susceptibility. However, past case-control studies showed inconsistent results. In Viet Nam, of 62 patients with SARS, 44 participated in the present study together with 103 individuals who had contact with SARS patients and 50 without contact history. HLA-DRB1*12 was more frequently shown in SARS patients than in controls (corrected p = 0.042). HLA-DRB1*1202, the predominant allele in the Vietnamese population showed the strongest association with SARS in a dominant model (corrected p = 0.0065 and 0.0052, depending on the controls to be compared). Our results and accumulated data on HLA in the Asian populations would help in the understanding of associations with emerging infectious diseases.
Asunto(s)
Polimorfismo Genético , Síndrome Respiratorio Agudo Grave/genética , Pueblo Asiatico/genética , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Antígenos HLA-DR/genética , Cadenas HLA-DRB1 , Humanos , Síndrome Respiratorio Agudo Grave/etnología , VietnamRESUMEN
We investigated a nosocomial infection of severe acute respiratory syndrome (SARS) in Vietnam in 2003 and attempted to identify risk factors for SARS infection. Of the 146 subjects who came into contact with SARS patients at Hospital A, 43 (29.5%) developed SARS, and an additional 16 (11%) were asymptomatic but SARS-coronavirus (CoV) seropositive. The asymptomatic infection rate accounted for 15.5% of the total number of infected patients at Hospital A, which was higher than that of 6.5% observed at Hospital B, to where all patients from Hospital A were eventually transported (P<0.05). At Hospital A, the risk for developing SARS was 12.6 times higher in individuals not using a mask than in those using a mask. The SARS epidemic in Vietnam resulted in numerous secondary infections due to its unknown etiology and delayed recognition at the beginning of the epidemic. The consistent and proper use of a mask was shown to be crucial for constant protection against infection with SARS.
Asunto(s)
Infección Hospitalaria/transmisión , Brotes de Enfermedades/prevención & control , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Síndrome Respiratorio Agudo Grave/transmisión , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Infección Hospitalaria/virología , Hospitales Generales , Humanos , Control de Infecciones/métodos , Máscaras/estadística & datos numéricos , Cuerpo Médico de Hospitales , Personal de Enfermería en Hospital , Personal de Hospital , Equipos de Seguridad/estadística & datos numéricos , Factores de Riesgo , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/prevención & control , Síndrome Respiratorio Agudo Grave/virología , Encuestas y Cuestionarios , VietnamRESUMEN
We analyzed genetic variations of angiotensin-converting enzyme 2 (ACE2), considering that it might influence patients' susceptibility to severe acute respiratory syndrome-associated coronavirus (SARS-CoV) or development of SARS as a functional receptor. By cloning of the full-length cDNA of the ACE2 gene in the lung, where replication occurs on SARS-CoV, it was shown that there are different splicing sites. All exons including the new alternative exon, exon-intron boundaries, and the corresponding 5'-flanking region of the gene were investigated and 19 single nucleotide polymorphisms (SNPs) were found. Out of these, 13 SNPs including one non-synonymous substitution and three 3'-UTR polymorphisms were newly identified. A case control study involving 44 SARS cases, 16 anti-SARS-CoV antibody-positive contacts, 87 antibody-negative contacts, and 50 non-contacts in Vietnam, failed to obtain any evidence that the ACE2 gene polymorphisms are involved in the disease process in the population. Nevertheless, identification of new 5'-untranslated exon and new SNPs is considered helpful in investigating regulation of ACE2 gene expression in the future.
Asunto(s)
Región de Flanqueo 5'/genética , Carboxipeptidasas/genética , Exones/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Alelos , Empalme Alternativo , Enzima Convertidora de Angiotensina 2 , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A , Polimorfismo de Nucleótido Simple , Síndrome Respiratorio Agudo Grave/enzimología , Síndrome Respiratorio Agudo Grave/genética , VietnamRESUMEN
We hypothesized that host antiviral genes induced by type I interferons might affect the natural course of severe acute respiratory syndrome (SARS). We analyzed single nucleotide polymorphisms (SNPs) of 2',5'-oligoadenylate synthetase 1 (OAS-1), myxovirus resistance-A (MxA), and double-stranded RNA-dependent protein kinase in 44 Vietnamese SARS patients with 103 controls. The G-allele of non-synonymous A/G SNP in exon 3 of OAS-1 gene showed association with SARS (p=0.0090). The G-allele in exon 3 of OAS-1 and the one in exon 6 were in strong linkage disequilibrium and both of them were associated with SARS infection. The GG genotype and G-allele of G/T SNP at position -88 in the MxA gene promoter were found more frequently in hypoxemic group than in non-hypoxemic group of SARS (p=0.0195). Our findings suggest that polymorphisms of two IFN-inducible genes OAS-1 and MxA might affect susceptibility to the disease and progression of SARS at each level.
Asunto(s)
2',5'-Oligoadenilato Sintetasa/genética , Proteínas de Unión al GTP/genética , Polimorfismo Genético/genética , Síndrome Respiratorio Agudo Grave/genética , Adolescente , Adulto , Anciano , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Proteínas de Resistencia a Mixovirus , VietnamRESUMEN
We have hypothesized that genetic predisposition influences the progression of SARS. Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases. This time, the polymorphism was genotyped in 44 Vietnamese SARS cases, with 103 healthy controls who had had a contact with the SARS patients and 50 controls without any contact history. SARS cases were divided into either non-hypoxemic or hypoxemic groups. Despite the small sample size, the frequency of the D allele was significantly higher in the hypoxemic group than in the non-hypoxemic group (p=0.013), whereas there was no significant difference between the SARS cases and controls, irrespective of a contact history. ACE1 might be one of the candidate genes that influence the progression of pneumonia in SARS.