RESUMEN
BACKGROUND: Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the genes involved in glutametergic transmission. We report here association studies of schizophrenia with SLC1A4, SLC1A5 encoding neutral amino acid transporters ASCT1, ASCT2, and SLC6A5, SLC6A9 encoding glycine transporters GLYT2, GLYT1, respectively. METHODS: We initially tested the association of 21 single nucleotide polymorphisms (SNPs) distributed in the four gene regions with schizophrenia using 100 Japanese cases-control pairs and examined allele, genotype and haplotype association with schizophrenia. The observed nominal significance were examined in the full-size samples (400 cases and 420 controls). RESULTS: We observed nominally significant single-marker associations with schizophrenia in SNP2 (P = 0.021) and SNP3 (P = 0.029) of SLC1A4, SNP1 (P = 0.009) and SNP2 (P = 0.022) of SLC6A5. We also observed nominally significant haplotype associations with schizophrenia in the combinations of SNP2-SNP7 (P = 0.037) of SLC1A4 and SNP1-SNP4 (P = 0.043) of SLC6A5. We examined all of the nominal significance in the Full-size Sample Set, except one haplotype with insufficient LD. The significant association of SNP1 of SLC6A5 with schizophrenia was confirmed in the Full-size Sample Set (P = 0.018). CONCLUSION: We concluded that at least one susceptibility locus for schizophrenia may be located within or nearby SLC6A5, whereas SLC1A4, SLC1A5 and SLC6A9 are unlikely to be major susceptibility genes for schizophrenia in the Japanese population.
Asunto(s)
Sistema de Transporte de Aminoácidos ASC/genética , Proteínas de Transporte de Glicina en la Membrana Plasmática/genética , Enfermedad de Hartnup/genética , Polimorfismo Genético/genética , Esquizofrenia/genética , Alelos , Estudios de Casos y Controles , Exones/genética , Femenino , Genotipo , Haplotipos , Enfermedad de Hartnup/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Antígenos de Histocompatibilidad Menor , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologíaRESUMEN
A biochemical screening programme for the detection of inherited metabolic disease was carried out on urine and blood samples from inmates of the Alexandra Institute for the mentally retarded, Cape Town. Of the 1087 patients screened, positive results for phenylketonuria were obtained in 3, for cystinuria in 2 and for Hartnup disease in 1. The overall frequency of metabolic disorders was 0,6%. It is evident that genetic metabolic disease as detected by current screening procedures makes only a small contribution to the overall burden of mental retardation.
Asunto(s)
Discapacidad Intelectual/complicaciones , Errores Innatos del Metabolismo/metabolismo , Adulto , Cistinuria/complicaciones , Cistinuria/epidemiología , Cistinuria/metabolismo , Femenino , Enfermedad de Hartnup/complicaciones , Enfermedad de Hartnup/epidemiología , Enfermedad de Hartnup/metabolismo , Humanos , Discapacidad Intelectual/epidemiología , Masculino , Tamizaje Masivo , Errores Innatos del Metabolismo/complicaciones , Persona de Mediana Edad , Mucopolisacaridosis/complicaciones , Mucopolisacaridosis/epidemiología , Mucopolisacaridosis/metabolismo , Fenilcetonurias/complicaciones , Fenilcetonurias/epidemiología , Fenilcetonurias/metabolismo , SudáfricaAsunto(s)
Población Negra , Enfermedad de Hartnup/epidemiología , Adolescente , Enfermedad de Hartnup/genética , Humanos , Masculino , Linaje , SenegalRESUMEN
Hartnup disease was diagnosed in 12 children and 3 of their 15 sibs in the course of routine urine screening of 6-week-old infants in New South Wales. These children were followed for up to 8 years, during which time there were only two clinical episodes which might be ascribed to Hartnup disease. The mental development of all the children was normal. 10 had height centiles less than the midparent height centiles, while 4 had centiles equal to or above the midparent centiles. The study shows that in children with Hartnup disease in Australia symptoms are very uncommon. Mental development is normal, and heights are possibly slightly below that expected. Hartnup disease has an incidence of approximately 1 in 33 000 in New South Wales.
