RESUMEN
A large-scale meta-analysis of 14 genome-wide association studies has identified and replicated a series of susceptibility polymorphisms for coronary artery disease (CAD) in European ancestry populations, but evidences for the associations of these loci with CAD in other ethnicities remain lacking. Herein we investigated the associations between ten (rs579459, rs12413409, rs964184, rs4773144, rs2895811, rs3825807, rs216172, rs12936587, rs46522 and rs3798220) of these loci and CAD in Southern Han Chinese (CHS). Genotyping was performed in 1716 CAD patients and 1572 controls using mass spectrography. Both allelic and genotypic associations of rs964184, rs2895811 and rs3798220 with CAD were significant, regardless of adjustment for covariates of gender, age, hypertension, type 2 diabetes, blood lipid profiles and smoking. Significant association of rs12413409 was initially not observed, but after the adjustment for the covariates, both allelic and genotypic associations were identified as significant. Neither allelic nor genotypic association of the other six polymorphisms with CAD was significant regardless of the adjustment. Our results indicated that four loci of the total 10 were associated with CAD in CHS. Therefore, some of the CAD-related loci in European ancestry populations are indeed susceptibility loci for the risk of CAD in Han Chinese.
Asunto(s)
Pueblo Asiatico/genética , Enfermedad de la Arteria Coronaria/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Alelos , Estudios de Casos y Controles , China , Enfermedad de la Arteria Coronaria/diagnóstico , Frecuencia de los Genes , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Oportunidad Relativa , RiesgoRESUMEN
The first genome-wide association study for coronary artery disease (CAD) in the Han Chinese population, we reported recently, had identified rs6903956 in gene ADTRP on chromosome 6p24.1 as a novel susceptibility locus for CAD. The risk allele of rs6903956 was associated with decreased mRNA expression of ADTRP. To further study the correlation of ADTRP expression and CAD, in this study we evaluated the associations of eight common variants in the expression-regulating regions of ADTRP with CAD in the Southern Han Chinese population. Rs169790 in 3'UTR, rs2076189 in 5'UTR, four SNPs (rs2076188, rs7753407, rs11966356 and rs1018383) in promoter, and two SNPs (rs3734273, rs80355771) in the last intron of ADTRP were genotyped in 1716 CAD patients and 1572 controls. The correlations between these loci and total or early-onset CAD were investigated. None of these loci was discovered to associate with total CAD (P > 0.05). However, with early-onset CAD, significant both allelic and genotypic associations of rs7753407, rs11966356 and rs1018383 were identified, after adjustment for risk factors of age, gender, hypertension, diabetes, lipid profiles and smoking (adjusted P < 0.05). A haplotype AGCG (constructed by rs2076188, rs7753407, rs11966356 and rs1018383) was identified to protect subjects from early-onset CAD (OR = 0.332, 95% CI = 0.105-0.879, adjusted P = 0.010). Real-time quantitative reverse transcription polymerase chain reaction assay showed that the risk alleles of the associated loci were significantly associated with decreased expression of ADTRP mRNA. Moreover, the average level of ADTRP mRNA expression in early-onset CAD cases was significantly lower than that in controls. Our results provide new evidence supporting the association of ADTRP with the pathogenesis of early-onset CAD.
Asunto(s)
Pueblo Asiatico/etnología , Enfermedad de la Arteria Coronaria/genética , Etnicidad/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Regiones no Traducidas 3'/genética , Regiones no Traducidas 5'/genética , Anciano , Pueblo Asiatico/genética , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad/genética , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: To explore the forensic pathological features of death caused by anaphylactic shock. METHODS: One hundred and forty-two death cases of anaphylactic shock were retrospectively analyzed. The IgE level in the serum of anaphylactic shock cases were statistically compared with that of 62 non-anaphylactic shock cases. RESULTS: Most cases (77.46%) of anaphylactic shock death occurred in the medical institutes, with intravenous drug administration accounting for 53.53% of anaphylactic shock death. ß-Lactam antibiotics, glucocorticoid and herbal medications were responsible for a significant proportion of such cases. Although characteristic histopathological changes were absent in vast majority of these anaphylactic shock cases, the differences of IgE levels in the serum between anaphylactic shock group and non-anaphylactic shock group were statistically significant (P<0.05). CONCLUSION: Combined information including clinical data, autopsy results, IgE level, and other specific test results should be evaluated together in the forensic pathological diagnosis of anaphylactic shock.
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Anafilaxia , Causas de Muerte , Patologia Forense , Autopsia , Humanos , Infusiones Intravenosas , Estudios Retrospectivos , SueroRESUMEN
Yunnan sudden death syndrome (YSDS) is an abruptly fatal disease of unknown etiology, found mostly in central or northwestern mountain area (with altitude between 1,815 and 2,225 meters) of Yunnan province from June to September every year. It occurs mostly in young female adults, with high incidences in Lisu, Yi and Miao ethnics and high familial aggregation. The clinical manifestation of YSDS is changeful and the pathological characteristic is lack of specificity. The pathogenesis may be attributed to several factors including poor hygiene and lower socioeconomic conditions, lack of Selenium or Chromium, infection of Coxsackie B virus, mushroom consumption and special geological conditions. This article reviews the epidemiologic features, clinical manifestations, pathological features, etiology and hypothesis in order to provide clues for the research of YSDS.
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Muerte Súbita , Adulto , China , Muerte Súbita/epidemiología , Muerte Súbita/etiología , Muerte Súbita/patología , Femenino , Humanos , SíndromeRESUMEN
The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation, facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.