RESUMEN
BACKGROUND: Autism is a neurodevelopmental disorder with a strong genetic background that has been suggested to be associated with a susceptibility gene, engrailed homeobox 2(EN2), which maps to chromosome 7q36. Our study was aimed to explore the association between EN2 intronic single nucleotide polymorphisms (SNPs) with autism in an ethnic Han Chinese population. METHODS: A total of 193 autism cases and 309 controls were recruited. Five SNPs including rs3824068, rs3824067, rs1861972, rs1861973 and rs3830031 in the intron 1 region were genotyped by using the TaqMan SNP assay. RESULTS: Both the allelic frequencies and genotype distribution of the EN2 intronic SNPs were found to have statistically significant differences between cases and controls, except rs1861972, rs3024067 and rs3824068. According to the constructed linkage disequilibrium plot using genotype data, it was suggested that further haplotypic analyses can be performed on rs3824068, rs1861972 and rs1861973. After completed analyses by the Unphased and Phase programs and logistic regression analysis, one 2-marker haplotype A-C (beta = -2.897; p = 0.013; OR = 0.055) and one 3-marker haplotype G-A-C (beta = -0.491; p = 0.015; OR = 0.612) were identified that were plausibly associated with autism in the ethnic Chinese population. CONCLUSIONS: The haplotype A-C of rs1861972 and rs1861973 is the core element of the observed haplotype association in this study, which plays a role as a protective factor against autism; in addition, the haplotype G-A-C is less frequent in male cases compared to controls (38.64 vs. 52.51%), which plausibly modulate disease vulnerability to autism. However, further evidence of the haplotype association of EN2 intronic SNPs and uncertain transcription factor interaction is warranted for further clarification.
Asunto(s)
Pueblo Asiatico/genética , Trastorno Autístico/genética , Predisposición Genética a la Enfermedad , Proteínas de Homeodominio/genética , Intrones/genética , Proteínas del Tejido Nervioso/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Pueblo Asiatico/etnología , Distribución de Chi-Cuadrado , Femenino , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Desequilibrio de Ligamiento , Modelos Logísticos , Masculino , Persona de Mediana EdadRESUMEN
Groups at seasonal risk for deliberate self-harm (DSH) vary according to their geographic location. It is unknown, however, if seasonal risk factors for DSH are associated with place of birth or place of residence as these are confounded in all studies to date. In order to disaggregate place of birth from place of residence we examined general and seasonal risk factors for DSH in three different population birth groups living in Western Australia: Australian Aborigines, Australian born non-Aborigines, and UK migrants. We found Aborigines are at much higher general risk for DSH than non-Aborigines, but are not at seasonal risk, whereas non-Aboriginal Australians and UK migrants are. For UK migrants, this is only found for females. For all groups at seasonal risk this peaks during the austral (southern hemisphere) spring/summer. Furthermore, non-Aboriginal Australians and UK migrants show a consistent pattern of increased case fatality with increasing age. In contrast, case fatality does not increase with age among Australian Aborigines. Overall, despite living in the same environment, the three birth groups show different patterns of seasonal risk for DSH. In particular, the sex difference found between UK migrants and non-Aboriginal Australian birth groups suggests that predisposition toward seasonal risk for DSH is established early in life, but when present this is expressed according to local conditions.
Asunto(s)
Emigrantes e Inmigrantes/estadística & datos numéricos , Nativos de Hawái y Otras Islas del Pacífico/estadística & datos numéricos , Características de la Residencia , Estaciones del Año , Medio Social , Intento de Suicidio/estadística & datos numéricos , Suicidio/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Causas de Muerte , Comparación Transcultural , Estudios Transversales , Humanos , Persona de Mediana Edad , Mortalidad , Factores de Riesgo , Factores Sexuales , Suicidio/etnología , Intento de Suicidio/etnología , Australia Occidental , Adulto JovenRESUMEN
A number of differences exist between the seasonality of suicide and suicidal behaviour. Case fatality is one index of the relationship between these phenomena. The purpose of this study was to use contemporaneous data to examine the impact of case fatality on the seasonality of suicidal behaviour. All deliberate self-harm (ICD9 E950-58) hospitalisations (DSH) and deaths (suicide) for 1984-93 were extracted from the Western Australia case register (N=22 883). Case fatality was calculated by method of suicide. Data were arranged in time series by standardised month according to case fatality; sex and age and analysed using spectral analysis. We found that DSH involving low case fatal methods is seasonal with a spring peak (95% confidence interval). The explained variance of the seasonal rhythm increases with age. Suicide involving high case fatal methods is not seasonal. The increase in DSH seasonality with age may be related to a parallel increase in case fatality.